Epigenetics in radiation-induced fibrosis (original) (raw)

• Thariat J, Hannoun-Levi JM, Sun Myint A, Vuong T, Gerard JP . Past, present, and future of radiotherapy for the benefit of patients. Nat Rev Clin Oncol 2013; 10: 52–60.
  Article CAS PubMed Google Scholar
• Sperk E, Welzel G, Keller A, Kraus-Tiefenbacher U, Gerhardt A, Sutterlin M et al. Late radiation toxicity after intraoperative radiotherapy (IORT) for breast cancer: results from the randomized phase III trial TARGIT A. Breast Cancer Res Treat 2012; 135: 253–260.
  Article PubMed Google Scholar
• Yarnold J, Brotons MC . Pathogenetic mechanisms in radiation fibrosis. Radiother Oncol 2010; 97: 149–161.
  Article CAS PubMed Google Scholar
• Popanda O, Marquardt JU, Chang-Claude J, Schmezer P . Genetic variation in normal tissue toxicity induced by ionizing radiation. Mutat Res 2009; 667: 58–69.
  Article CAS PubMed Google Scholar
• Chang-Claude J, Ambrosone CB, Lilla C, Kropp S, Helmbold I, von Fournier D et al. Genetic polymorphisms in DNA repair and damage response genes and late normal tissue complications of radiotherapy for breast cancer. Br J Cancer 2009; 100: 1680–1686.
  Article CAS PubMed PubMed Central Google Scholar
• Andreassen CN, Alsner J . Genetic variants and normal tissue toxicity after radiotherapy: a systematic review. Radiother Oncol 2009; 92: 299–309.
  Article CAS PubMed Google Scholar
• Cheresh P, Kim SJ, Tulasiram S, Kamp DW . Oxidative stress and pulmonary fibrosis. Biochim Biophys Acta 2013; 1832: 1028–1040.
  Article CAS PubMed Google Scholar
• Amundson SA, Bittner M, Fornace AJ Jr. . Functional genomics as a window on radiation stress signaling. Oncogene 2003; 22: 5828–5833.
  Article CAS PubMed Google Scholar
• Bird A . Perceptions of epigenetics. Nature 2007; 447: 396–398.
  Article CAS PubMed Google Scholar
• Esteller M . Non-coding RNAs in human disease. Nat Rev Genet 2011; 12: 861–874.
  CAS PubMed Google Scholar
• Jones PA . Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 2012; 13: 484–492.
  Article CAS PubMed Google Scholar
• Zvaifler NJ . Relevance of the stroma and epithelial-mesenchymal transition (EMT) for the rheumatic diseases. Arthritis Res Ther 2006; 8: 210.
  Article PubMed PubMed Central Google Scholar
• Krenning G, Zeisberg EM, Kalluri R . The origin of fibroblasts and mechanism of cardiac fibrosis. J Cell Physiol 2010; 225: 631–637.
  Article CAS PubMed PubMed Central Google Scholar
• Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML, Gabbiani G . The myofibroblast: one function, multiple origins. Am J Pathol 2007; 170: 1807–1816.
  Article CAS PubMed PubMed Central Google Scholar
• Bielefeld KA, Amini-Nik S, Alman BA . Cutaneous wound healing: recruiting developmental pathways for regeneration. Cell Mol Life Sci 2013; 70: 2059–2081.
  Article CAS PubMed Google Scholar
• Wynn TA . Cellular and molecular mechanisms of fibrosis. J Pathol 2008; 214: 199–210.
  Article CAS PubMed PubMed Central Google Scholar
• Pohlers D, Brenmoehl J, Loffler I, Muller CK, Leipner C, Schultze-Mosgau S et al. TGF-beta and fibrosis in different organs - molecular pathway imprints. Biochim Biophys Acta 2009; 1792: 746–756.
  Article CAS PubMed Google Scholar
• Kruse JJ, Floot BG, te Poele JA, Russell NS, Stewart FA . Radiation-induced activation of TGF-beta signaling pathways in relation to vascular damage in mouse kidneys. Radiat Res 2009; 171: 188–197.
  Article CAS PubMed Google Scholar
• Milliat F, Francois A, Isoir M, Deutsch E, Tamarat R, Tarlet G et al. Influence of endothelial cells on vascular smooth muscle cells phenotype after irradiation: implication in radiation-induced vascular damages. Am J Pathol 2006; 169: 1484–1495.
  Article CAS PubMed PubMed Central Google Scholar
• Gaugler MH, Vereycken-Holler V, Squiban C, Vandamme M, Vozenin-Brotons MC, Benderitter M . Pravastatin limits endothelial activation after irradiation and decreases the resulting inflammatory and thrombotic responses. Radiat Res 2005; 163: 479–487.
  Article CAS PubMed Google Scholar
• Xiao C, Wang RH, Lahusen TJ, Park O, Bertola A, Maruyama T et al. Progression of chronic liver inflammation and fibrosis driven by activation of c-JUN signaling in Sirt6 mutant mice. J Biol Chem 2012; 287: 41903–41913.
  Article CAS PubMed PubMed Central Google Scholar
• Ruiz-Ortega M, Rodriguez-Vita J, Sanchez-Lopez E, Carvajal G, Egido J . TGF-beta signaling in vascular fibrosis. Cardiovasc Res 2007; 74: 196–206.
  Article CAS PubMed Google Scholar
• Fujii H, Kawada N . Inflammation and fibrogenesis in steatohepatitis. J Gastroenterol 2012; 47: 215–225.
  Article CAS PubMed Google Scholar
• Li C, Wilson PB, Levine E, Barber J, Stewart AL, Kumar S . TGF-beta1 levels in pre-treatment plasma identify breast cancer patients at risk of developing post-radiotherapy fibrosis. Int J Cancer 1999; 84: 155–159.
  Article CAS PubMed Google Scholar
• Westbury CB, Yarnold JR . Radiation fibrosis—current clinical and therapeutic perspectives. Clin Oncol (R Coll Radiol) 2012; 24: 657–672.
  Article CAS Google Scholar
• Haydont V, Riser BL, Aigueperse J, Vozenin-Brotons MC . Specific signals involved in the long-term maintenance of radiation-induced fibrogenic differentiation: a role for CCN2 and low concentration of TGF-beta1. Am J Physiol Cell Physiol 2008; 294: C1332–C1341.
  Article CAS PubMed Google Scholar
• Hu S, Chen Y, Li L, Chen J, Wu B, Zhou X et al. Effects of adenovirus-mediated delivery of the human hepatocyte growth factor gene in experimental radiation-induced heart disease. Int J Radiat Oncol Biol Phys 2009; 75: 1537–1544.
  Article CAS PubMed Google Scholar
• Gottlober P, Steinert M, Bahren W, Weber L, Gerngross H, Peter RU . Interferon-gamma in 5 patients with cutaneous radiation syndrome after radiation therapy. Int J Radiat Oncol Biol Phys 2001; 50: 159–166.
  Article CAS PubMed Google Scholar
• Puthawala K, Hadjiangelis N, Jacoby SC, Bayongan E, Zhao Z, Yang Z et al. Inhibition of integrin alpha(v)beta6, an activator of latent transforming growth factor-beta, prevents radiation-induced lung fibrosis. Am J Respir Crit Care Med 2008; 177: 82–90.
  Article CAS PubMed Google Scholar
• Daugherity EK, Balmus G, Al Saei A, Moore ES, Abi Abdallah D, Rogers AB et al. The DNA damage checkpoint protein ATM promotes hepatocellular apoptosis and fibrosis in a mouse model of non-alcoholic fatty liver disease. Cell Cycle 2012; 11: 1918–1928.
  Article CAS PubMed PubMed Central Google Scholar
• Haase MG, Klawitter A, Bierhaus A, Yokoyama KK, Kasper M, Geyer P et al. Inactivation of AP1 proteins by a nuclear serine protease precedes the onset of radiation-induced fibrosing alveolitis. Radiat Res 2008; 169: 531–542.
  Article CAS PubMed Google Scholar
• Zhao W, Robbins ME . Inflammation and chronic oxidative stress in radiation-induced late normal tissue injury: therapeutic implications. Curr Med Chem 2009; 16: 130–143.
  Article CAS PubMed Google Scholar
• Veldwijk MR, Herskind C, Sellner L, Radujkovic A, Laufs S, Fruehauf S et al. Normal-tissue radioprotection by overexpression of the copper-zinc and manganese superoxide dismutase genes. Strahlenther Onkol 2009; 185: 517–523.
  Article PubMed Google Scholar
• Moding EJ, Kastan MB, Kirsch DG . Strategies for optimizing the response of cancer and normal tissues to radiation. Nat Rev Drug Discov 2013; 12: 526–542.
  Article CAS PubMed PubMed Central Google Scholar
• Freitinger Skalicka Z, Zolzer F, Beranek L, Racek J . Indicators of oxidative stress after ionizing and/or non-ionizing radiation: superoxid dismutase and malondialdehyde. J Photochem Photobiol B 2012; 117: 111–114.
  Article CAS PubMed Google Scholar
• Pandita TK, Richardson C . Chromatin remodeling finds its place in the DNA double-strand break response. Nucleic Acids Res 2009; 37: 1363–1377.
  Article CAS PubMed PubMed Central Google Scholar
• Rossetto D, Truman AW, Kron SJ, Cote J . Epigenetic modifications in double-strand break DNA damage signaling and repair. Clin Cancer Res 2010; 16: 4543–4552.
  Article CAS PubMed PubMed Central Google Scholar
• Koturbash I, Baker M, Loree J, Kutanzi K, Hudson D, Pogribny I et al. Epigenetic dysregulation underlies radiation-induced transgenerational genome instability in vivo. Int J Radiat Oncol Biol Phys 2006; 66: 327–330.
  Article CAS PubMed Google Scholar
• Koturbash I, Rugo RE, Hendricks CA, Loree J, Thibault B, Kutanzi K et al. Irradiation induces DNA damage and modulates epigenetic effectors in distant bystander tissue in vivo. Oncogene 2006; 25: 4267–4275.
  Article CAS PubMed Google Scholar
• Dickey JS, Baird BJ, Redon CE, Sokolov MV, Sedelnikova OA, Bonner WM . Intercellular communication of cellular stress monitored by gamma-H2AX induction. Carcinogenesis 2009; 30: 1686–1695.
  Article CAS PubMed PubMed Central Google Scholar
• Coppes RP, van der Goot A, Lombaert IM . Stem cell therapy to reduce radiation-induced normal tissue damage. Semin Radiat Oncol 2009; 19: 112–121.
  Article PubMed Google Scholar
• Mothersill C, Seymour C . Are epigenetic mechanisms involved in radiation-induced bystander effects? Front Genet 2012; 3: 74.
  Article PubMed PubMed Central Google Scholar
• Kuhmann C, Weichenhan D, Rehli M, Plass C, Schmezer P, Popanda O . DNA methylation changes in cells regrowing after fractioned ionizing radiation. Radiother Oncol 2011; 101: 116–121.
  Article CAS PubMed Google Scholar
• Sanders YY, Ambalavanan N, Halloran B, Zhang X, Liu H, Crossman DK et al. Altered DNA methylation profile in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2012; 186: 525–535.
  Article CAS PubMed PubMed Central Google Scholar
• Rabinovich EI, Kapetanaki MG, Steinfeld I, Gibson KF, Pandit KV, Yu G et al. Global methylation patterns in idiopathic pulmonary fibrosis. PLoS ONE 2012; 7: e33770.
  Article CAS PubMed PubMed Central Google Scholar
• Komatsu Y, Waku T, Iwasaki N, Ono W, Yamaguchi C, Yanagisawa J . Global analysis of DNA methylation in early-stage liver fibrosis. BMC Med Genomics 2012; 5: 5.
  Article CAS PubMed PubMed Central Google Scholar
• Yang JJ, Tao H, Huang C, Shi KH, Ma TT, Bian EB et al. DNA methylation and MeCP2 regulation of PTCH1 expression during rats hepatic fibrosis. Cell Signal 2013; 25: 1202–1211.
  Article CAS PubMed Google Scholar
• Zeisberg EM, Zeisberg M . The role of promoter hypermethylation in fibroblast activation and fibrogenesis. J Pathol 2013; 229: 264–273.
  Article CAS PubMed Google Scholar
• Bechtel W, McGoohan S, Zeisberg EM, Muller GA, Kalbacher H, Salant DJ et al. Methylation determines fibroblast activation and fibrogenesis in the kidney. Nat Med 2010; 16: 544–550.
  Article CAS PubMed PubMed Central Google Scholar
• Jones PA, Liang G . Rethinking how DNA methylation patterns are maintained. Nat Rev Genet 2009; 10: 805–811.
  Article CAS PubMed PubMed Central Google Scholar
• Wang Y, Fan PS, Kahaleh B . Association between enhanced type I collagen expression and epigenetic repression of the FLI1 gene in scleroderma fibroblasts. Arthritis Rheum 2006; 54: 2271–2279.
  Article CAS PubMed Google Scholar
• Sun CY, Chang SC, Wu MS . Suppression of Klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation. Kidney Int 2012; 81: 640–650.
  Article CAS PubMed PubMed Central Google Scholar
• Bian EB, Huang C, Ma TT, Tao H, Zhang H, Cheng C et al. DNMT1-mediated PTEN hypermethylation confers hepatic stellate cell activation and liver fibrogenesis in rats. Toxicol Appl Pharmacol 2012; 264: 13–22.
  Article CAS PubMed Google Scholar
• Hu B, Gharaee-Kermani M, Wu Z, Phan SH . Epigenetic regulation of myofibroblast differentiation by DNA methylation. Am J Pathol 2010; 177: 21–28.
  Article CAS PubMed PubMed Central Google Scholar
• Weichenhan D, Plass C . The evolving epigenome. Hum Mol Genet 2013; 22: R1–R6.
  Article CAS PubMed Google Scholar
• Huang N, Tan L, Xue Z, Cang J, Wang H . Reduction of DNA hydroxymethylation in the mouse kidney insulted by ischemia reperfusion. Biochem Biophys Res Commun 2012; 422: 697–702.
  Article CAS PubMed Google Scholar
• Tampe B, Tampe D, Muller CA, Sugimoto H, Lebleu V, Xu X et al. Tet3-mediated hydroxymethylation of epigenetically silenced genes contributes to bone morphogenic protein 7-induced reversal of kidney fibrosis. J Am Soc Nephrol 2014; 25: 905–912.
  Article CAS PubMed PubMed Central Google Scholar
• Bian EB, Huang C, Wang H, Chen XX, Tao H, Zhang L et al. The role of methyl-CpG binding protein 2 in liver fibrosis. Toxicology 2013; 309: 9–14.
  Article CAS PubMed Google Scholar
• Mann J, Chu DC, Maxwell A, Oakley F, Zhu NL, Tsukamoto H et al. MeCP2 controls an epigenetic pathway that promotes myofibroblast transdifferentiation and fibrosis. Gastroenterology 2010; 138: 705–714 714 e701-704.
  Article CAS PubMed Google Scholar
• Zhu NL, Asahina K, Wang J, Ueno A, Lazaro R, Miyaoka Y et al. Hepatic stellate cell-derived delta-like homolog 1 (DLK1) protein in liver regeneration. J Biol Chem 2012; 287: 10355–10367.
  Article CAS PubMed PubMed Central Google Scholar
• Tao H, Huang C, Yang JJ, Ma TT, Bian EB, Zhang L et al. MeCP2 controls the expression of RASAL1 in the hepatic fibrosis in rats. Toxicology 2011; 290: 327–333.
  Article PubMed CAS Google Scholar
• Suzuki M, Yamada T, Kihara-Negishi F, Sakurai T, Oikawa T . Direct association between PU.1 and MeCP2 that recruits mSin3A-HDAC complex for PU.1-mediated transcriptional repression. Oncogene 2003; 22: 8688–8698.
  Article CAS PubMed Google Scholar
• Hu B, Gharaee-Kermani M, Wu Z, Phan SH . Essential role of MeCP2 in the regulation of myofibroblast differentiation during pulmonary fibrosis. Am J Pathol 2011; 178: 1500–1508.
  Article CAS PubMed PubMed Central Google Scholar
• Maunakea AK, Chepelev I, Cui K, Zhao K . Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition. Cell Res 2013; 23: 1256–1269.
  Article CAS PubMed PubMed Central Google Scholar
• Asuthkar S, Velpula KK, Chetty C, Gorantla B, Rao JS . Epigenetic regulation of miRNA-211 by MMP-9 governs glioma cell apoptosis, chemosensitivity and radiosensitivity. Oncotarget 2012; 3: 1439–1454.
  Article PubMed PubMed Central Google Scholar
• Rivera AL, Pelloski CE, Gilbert MR, Colman H, De La Cruz C, Sulman EP et al. MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma. Neuro Oncol 2010; 12: 116–121.
  Article CAS PubMed Google Scholar
• Kim EH, Park AK, Dong SM, Ahn JH, Park WY . Global analysis of CpG methylation reveals epigenetic control of the radiosensitivity in lung cancer cell lines. Oncogene 2010; 29: 4725–4731.
  Article CAS PubMed Google Scholar
• Hofstetter B, Niemierko A, Forrer C, Benhattar J, Albertini V, Pruschy M et al. Impact of genomic methylation on radiation sensitivity of colorectal carcinoma. Int J Radiat Oncol Biol Phys 2010; 76: 1512–1519.
  Article CAS PubMed Google Scholar
• De Schutter H, Kimpe M, Isebaert S, Nuyts S . A systematic assessment of radiation dose enhancement by 5-Aza-2'-deoxycytidine and histone deacetylase inhibitors in head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys 2009; 73: 904–912.
  Article CAS PubMed Google Scholar
• Kumar A, Rai PS, Upadhya R, Vishwanatha, Prasada KS, Rao BS et al. Gamma-radiation induces cellular sensitivity and aberrant methylation in human tumor cell lines. Int J Radiat Biol 2011; 87: 1086–1096.
  Article CAS PubMed Google Scholar
• Antwih DA, Gabbara KM, Lancaster WD, Ruden DM, Zielske SP . Radiation-induced epigenetic DNA methylation modification of radiation-response pathways. Epigenetics 2013; 8: 839–848.
  Article CAS PubMed PubMed Central Google Scholar
• Kaup S, Grandjean V, Mukherjee R, Kapoor A, Keyes E, Seymour CB et al. Radiation-induced genomic instability is associated with DNA methylation changes in cultured human keratinocytes. Mutat Res 2006; 597: 87–97.
  Article CAS PubMed Google Scholar
• Lahtz C, Bates SE, Jiang Y, Li AX, Wu X, Hahn MA et al. Gamma irradiation does not induce detectable changes in DNA methylation directly following exposure of human cells. PLoS ONE 2012; 7: e44858.
  Article CAS PubMed PubMed Central Google Scholar
• Chaudhry MA, Omaruddin RA . Differential DNA methylation alterations in radiation-sensitive and -resistant cells. DNA Cell Biol 2012; 31: 908–916.
  Article CAS PubMed Google Scholar
• Koturbash I, Boyko A, Rodriguez-Juarez R, McDonald RJ, Tryndyak VP, Kovalchuk I et al. Role of epigenetic effectors in maintenance of the long-term persistent bystander effect in spleen in vivo. Carcinogenesis 2007; 28: 1831–1838.
  Article CAS PubMed Google Scholar
• Prunotto M, Budd DC, Gabbiani G, Meier M, Formentini I, Hartmann G et al. Epithelial-mesenchymal crosstalk alteration in kidney fibrosis. J Pathol 2012; 228: 131–147.
  Article CAS PubMed Google Scholar
• Pogribny I, Koturbash I, Tryndyak V, Hudson D, Stevenson SM, Sedelnikova O et al. Fractionated low-dose radiation exposure leads to accumulation of DNA damage and profound alterations in DNA and histone methylation in the murine thymus. Mol Cancer Res 2005; 3: 553–561.
  Article CAS PubMed Google Scholar
• Rugo RE, Mutamba JT, Mohan KN, Yee T, Chaillet JR, Greenberger JS et al. Methyltransferases mediate cell memory of a genotoxic insult. Oncogene 2011; 30: 751–756.
  Article CAS PubMed Google Scholar
• Armstrong CA, Jones GD, Anderson R, Iyer P, Narayanan D, Sandhu J et al. DNMTs are required for delayed genome instability caused by radiation. Epigenetics 2012; 7: 892–902.
  Article CAS PubMed PubMed Central Google Scholar
• Bauersachs J . Regulation of myocardial fibrosis by MicroRNAs. J Cardiovasc Pharmacol 2010; 56: 454–459.
  Article CAS PubMed Google Scholar
• Jiang X, Tsitsiou E, Herrick SE, Lindsay MA . MicroRNAs and the regulation of fibrosis. FEBS J 2010; 277: 2015–2021.
  Article CAS PubMed PubMed Central Google Scholar
• Dai Y, Khaidakov M, Wang X, Ding Z, Su W, Price E et al. MicroRNAs involved in the regulation of postischemic cardiac fibrosis. Hypertension 2013; 61: 751–756.
  Article CAS PubMed Google Scholar
• Pandit KV, Milosevic J, Kaminski N . MicroRNAs in idiopathic pulmonary fibrosis. Transl Res 2011; 157: 191–199.
  Article CAS PubMed Google Scholar
• Patel V, Noureddine L . MicroRNAs and fibrosis. Curr Opin Nephrol Hypertens 2012; 21: 410–416.
  Article CAS PubMed PubMed Central Google Scholar
• Srivastava SP, Koya D, Kanasaki K . MicroRNAs in kidney fibrosis and diabetic nephropathy: roles on EMT and EndMT. Biomed Res Int 2013; 2013: 125469.
  Article PubMed PubMed Central CAS Google Scholar
• He Y, Huang C, Zhang SP, Sun X, Long XR, Li J . The potential of microRNAs in liver fibrosis. Cell Signal 2012; 24: 2268–2272.
  Article CAS PubMed Google Scholar
• Bowen T, Jenkins RH, Fraser DJ . MicroRNAs, transforming growth factor beta-1, and tissue fibrosis. J Pathol 2013; 229: 274–285.
  Article CAS PubMed Google Scholar
• Metheetrairut C, Slack FJ . MicroRNAs in the ionizing radiation response and in radiotherapy. Curr Opin Genet Dev 2013; 23: 12–19.
  Article CAS PubMed PubMed Central Google Scholar
• Dickey JS, Zemp FJ, Martin OA, Kovalchuk O . The role of miRNA in the direct and indirect effects of ionizing radiation. Radiat Environ Biophys 2011; 50: 491–499.
  Article CAS PubMed Google Scholar
• Zhao L, Lu X, Cao Y . MicroRNA and signal transduction pathways in tumor radiation response. Cell Signal 2013; 25: 1625–1634.
  Article CAS PubMed PubMed Central Google Scholar
• Xiao F, Zuo Z, Cai G, Kang S, Gao X, Li T . miRecords: an integrated resource for microRNA-target interactions. Nucleic Acids Res 2009; 37: D105–D110.
  Article CAS PubMed Google Scholar
• Lakner AM, Steuerwald NM, Walling TL, Ghosh S, Li T, McKillop IH et al. Inhibitory effects of microRNA 19b in hepatic stellate cell-mediated fibrogenesis. Hepatology 2012; 56: 300–310.
  Article CAS PubMed Google Scholar
• Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 2008; 10: 593–601.
  Article CAS PubMed Google Scholar
• Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 2008; 456: 980–984.
  Article CAS PubMed Google Scholar
• Roderburg C, Urban GW, Bettermann K, Vucur M, Zimmermann H, Schmidt S et al. Micro-RNA profiling reveals a role for miR-29 in human and murine liver fibrosis. Hepatology 2011; 53: 209–218.
  Article CAS PubMed Google Scholar
• Bernardo BC, Gao XM, Winbanks CE, Boey EJ, Tham YK, Kiriazis H et al. Therapeutic inhibition of the miR-34 family attenuates pathological cardiac remodeling and improves heart function. Proc Natl Acad Sci USA 2012; 109: 17615–17620.
  Article CAS PubMed PubMed Central Google Scholar
• Volkmann I, Kumarswamy R, Pfaff N, Fiedler J, Dangwal S, Holzmann A et al. MicroRNA-mediated epigenetic silencing of sirtuin1 contributes to impaired angiogenic responses. Circ Res 2013; 113: 997–1003.
  Article CAS PubMed Google Scholar
• Mayr C, Hemann MT, Bartel DP . Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science 2007; 315: 1576–1579.
  Article CAS PubMed PubMed Central Google Scholar
• Pandit KV, Corcoran D, Yousef H, Yarlagadda M, Tzouvelekis A, Gibson KF et al. Inhibition and role of let-7d in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2010; 182: 220–229.
  Article CAS PubMed PubMed Central Google Scholar
• Sequeira-Lopez ML, Weatherford ET, Borges GR, Monteagudo MC, Pentz ES, Harfe BD et al. The microRNA-processing enzyme dicer maintains juxtaglomerular cells. J Am Soc Nephrol 2010; 21: 460–467.
  Article CAS PubMed PubMed Central Google Scholar
• Nawroth I, Alsner J, Deleuran BW, Dagnaes-Hansen F, Yang C, Horsman MR et al. Peritoneal macrophages mediated delivery of chitosan/siRNA nanoparticle to the lesion site in a murine radiation-induced fibrosis model. Acta Oncol 2013; 52: 1730–1738.
  Article CAS PubMed Google Scholar
• Stone HB . Leg contracture in mice: an assay of normal tissue response. Int J Radiat Oncol Biol Phys 1984; 10: 1053–1061.
  Article CAS PubMed Google Scholar
• Chung YL, Wang AJ, Yao LF . Antitumor histone deacetylase inhibitors suppress cutaneous radiation syndrome: implications for increasing therapeutic gain in cancer radiotherapy. Mol Cancer Ther 2004; 3: 317–325.
  CAS PubMed Google Scholar
• Purrucker JC, Fricke A, Ong MF, Rube C, Rube CE, Mahlknecht U . HDAC inhibition radiosensitizes human normal tissue cells and reduces DNA double-strand break repair capacity. Oncol Rep 2010; 23: 263–269.
  CAS PubMed Google Scholar
• Kramer M, Dees C, Huang J, Schlottmann I, Palumbo-Zerr K, Zerr P et al. Inhibition of H3K27 histone trimethylation activates fibroblasts and induces fibrosis. Ann Rheum Dis 2013; 72: 614–620.
  Article PubMed CAS Google Scholar
• Perugorria MJ, Wilson CL, Zeybel M, Walsh M, Amin S, Robinson S et al. Histone methyltransferase ASH1 orchestrates fibrogenic gene transcription during myofibroblast transdifferentiation. Hepatology 2012; 56: 1129–1139.
  Article CAS PubMed Google Scholar
• Sun G, Reddy MA, Yuan H, Lanting L, Kato M, Natarajan R . Epigenetic histone methylation modulates fibrotic gene expression. J Am Soc Nephrol 2010; 21: 2069–2080.
  Article CAS PubMed PubMed Central Google Scholar
• Zager RA, Johnson AC . Renal ischemia-reperfusion injury upregulates histone-modifying enzyme systems and alters histone expression at proinflammatory/profibrotic genes. Am J Physiol Renal Physiol 2009; 296: F1032–F1041.
  Article CAS PubMed PubMed Central Google Scholar
• Abrass CK, Hansen K, Popov V, Denisenko O . Alterations in chromatin are associated with increases in collagen III expression in aging nephropathy. Am J Physiol Renal Physiol 2011; 300: F531–F539.
  Article CAS PubMed Google Scholar
• Zeybel M, Hardy T, Wong YK, Mathers JC, Fox CR, Gackowska A et al. Multigenerational epigenetic adaptation of the hepatic wound-healing response. Nat Med 2012; 18: 1369–1377.
  Article CAS PubMed PubMed Central Google Scholar
• Tang X, Peng R, Ren Y, Apparsundaram S, Deguzman J, Bauer CM et al. BET bromodomain proteins mediate downstream signaling events following growth factor stimulation in human lung fibroblasts and are involved in bleomycin-induced pulmonary fibrosis. Mol Pharmacol 2013; 83: 283–293.
  Article CAS PubMed Google Scholar
• Ramadoss S, Chen X, Wang CY . Histone demethylase KDM6B promotes epithelial-mesenchymal transition. J Biol Chem 2012; 287: 44508–44517.
  Article CAS PubMed PubMed Central Google Scholar
• Ghosh AK, Varga J . The transcriptional coactivator and acetyltransferase p300 in fibroblast biology and fibrosis. J Cell Physiol 2007; 213: 663–671.
  Article CAS PubMed Google Scholar
• Ghosh AK, Bhattacharyya S, Varga J . The tumor suppressor p53 abrogates Smad-dependent collagen gene induction in mesenchymal cells. J Biol Chem 2004; 279: 47455–47463.
  Article CAS PubMed Google Scholar
• Bhattacharyya S, Ghosh AK, Pannu J, Mori Y, Takagawa S, Chen G et al. Fibroblast expression of the coactivator p300 governs the intensity of profibrotic response to transforming growth factor beta. Arthritis Rheum 2005; 52: 1248–1258.
  Article CAS PubMed Google Scholar
• Oliva J, Dedes J, Li J, French SW, Bardag-Gorce F . Epigenetics of proteasome inhibition in the liver of rats fed ethanol chronically. World J Gastroenterol 2009; 15: 705–712.
  Article CAS PubMed PubMed Central Google Scholar
• Kalash R, Berhane H, Au J, Rhieu BH, Epperly MW, Goff J et al. Differences in irradiated lung gene transcription between fibrosis-prone C57BL/6NHsd and fibrosis-resistant C3H/HeNHsd mice. In Vivo 2014; 28: 147–171.
  CAS PubMed Google Scholar
• Qin L, Han YP . Epigenetic repression of matrix metalloproteinases in myofibroblastic hepatic stellate cells through histone deacetylases 4: implication in tissue fibrosis. Am J Pathol 2010; 177: 1915–1928.
  Article CAS PubMed PubMed Central Google Scholar
• Vakhrusheva O, Smolka C, Gajawada P, Kostin S, Boettger T, Kubin T et al. Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice. Circ Res 2008; 102: 703–710.
  Article CAS PubMed Google Scholar
• Hromas R, Williamson EA, Fnu S, Lee YJ, Park SJ, Beck BD et al. Chk1 phosphorylation of Metnase enhances DNA repair but inhibits replication fork restart. Oncogene 2012; 31: 4245–4254.
  Article CAS PubMed PubMed Central Google Scholar
• Nguyen AT, Xiao B, Neppl RL, Kallin EM, Li J, Chen T et al. DOT1L regulates dystrophin expression and is critical for cardiac function. Genes Dev 2011; 25: 263–274.
  Article CAS PubMed PubMed Central Google Scholar
• Dong Q, Oh JE, Chen W, Kim R, Kim RH, Shin KH et al. Radioprotective effects of Bmi-1 involve epigenetic silencing of oxidase genes and enhanced DNA repair in normal human keratinocytes. J Invest Dermatol 2011; 131: 1216–1225.
  Article CAS PubMed Google Scholar
• Li X, Corsa CA, Pan PW, Wu L, Ferguson D, Yu X et al. MOF and H4 K16 acetylation play important roles in DNA damage repair by modulating recruitment of DNA damage repair protein Mdc1. Mol Cell Biol 2010; 30: 5335–5347.
  Article CAS PubMed PubMed Central Google Scholar
• Tjeertes JV, Miller KM, Jackson SP . Screen for DNA-damage-responsive histone modifications identifies H3K9Ac and H3K56Ac in human cells. EMBO J 2009; 28: 1878–1889.
  Article CAS PubMed PubMed Central Google Scholar
• Price BD, D'Andrea AD . Chromatin remodeling at DNA double-strand breaks. Cell 2013; 152: 1344–1354.
  Article CAS PubMed PubMed Central Google Scholar
• FitzGerald J, Moureau S, Drogaris P, O'Connell E, Abshiru N, Verreault A et al. Regulation of the DNA damage response and gene expression by the Dot1L histone methyltransferase and the 53Bp1 tumour suppressor. PLoS ONE 2011; 6: e14714.
  Article CAS PubMed PubMed Central Google Scholar
• Fnu S, Williamson EA, De Haro LP, Brenneman M, Wray J, Shaheen M et al. Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining. Proc Natl Acad Sci USA 2011; 108: 540–545.
  Article CAS PubMed Google Scholar
• Goodarzi AA, Kurka T, Jeggo PA . KAP-1 phosphorylation regulates CHD3 nucleosome remodeling during the DNA double-strand break response. Nat Struct Mol Biol 2011; 18: 831–839.
  Article CAS PubMed Google Scholar
• Guo CY, Mizzen C, Wang Y, Larner JM . Histone H1 and H3 dephosphorylation are differentially regulated by radiation-induced signal transduction pathways. Cancer Res 2000; 60: 5667–5672.
  CAS PubMed Google Scholar
• Gupta A, Sharma GG, Young CS, Agarwal M, Smith ER, Paull TT et al. Involvement of human MOF in ATM function. Mol Cell Biol 2005; 25: 5292–5305.
  Article CAS PubMed PubMed Central Google Scholar
• Huen MS, Grant R, Manke I, Minn K, Yu X, Yaffe MB et al. RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell 2007; 131: 901–914.
  Article CAS PubMed PubMed Central Google Scholar
• Li DQ, Ohshiro K, Reddy SD, Pakala SB, Lee MH, Zhang Y et al. E3 ubiquitin ligase COP1 regulates the stability and functions of MTA1. Proc Natl Acad Sci USA 2009; 106: 17493–17498.
  Article CAS PubMed PubMed Central Google Scholar
• Ogiwara H, Ui A, Otsuka A, Satoh H, Yokomi I, Nakajima S et al. Histone acetylation by CBP and p300 at double-strand break sites facilitates SWI/SNF chromatin remodeling and the recruitment of non-homologous end joining factors. Oncogene 2011; 30: 2135–2146.
  Article CAS PubMed Google Scholar
• Penicud K, Behrens A . DMAP1 is an essential regulator of ATM activity and function. Oncogene 2013; 33: 525–531.
  Article PubMed PubMed Central CAS Google Scholar
• Chailleux C, Tyteca S, Papin C, Boudsocq F, Puget N, Courilleau C et al. Physical interaction between the histone acetyl transferase Tip60 and the DNA double-strand breaks sensor MRN complex. Biochem J 2010; 426: 365–371.
  Article CAS PubMed Google Scholar
• Sun Y, Jiang X, Chen S, Fernandes N, Price BD . A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM. Proc Natl Acad Sci USA 2005; 102: 13182–13187.
  Article CAS PubMed PubMed Central Google Scholar
• Chernikova SB, Dorth JA, Razorenova OV, Game JC, Brown JM . Deficiency in Bre1 impairs homologous recombination repair and cell cycle checkpoint response to radiation damage in mammalian cells. Radiat Res 2010; 174: 558–565.
  Article CAS PubMed PubMed Central Google Scholar
• Wu J, Chen Y, Lu LY, Wu Y, Paulsen MT, Ljungman M et al. Chfr and RNF8 synergistically regulate ATM activation. Nat Struct Mol Biol 2011; 18: 761–768.
  Article CAS PubMed PubMed Central Google Scholar
• Niemantsverdriet M, de Jong E, Langendijk JA, Kampinga HH, Coppes RP . Synergistic induction of profibrotic PAI-1 by TGF-beta and radiation depends on p53. Radiother Oncol 2010; 97: 33–35.
  Article CAS PubMed Google Scholar
• Zhu F, Li Y, Zhang J, Piao C, Liu T, Li HH et al. Senescent cardiac fibroblast is critical for cardiac fibrosis after myocardial infarction. PLoS ONE 2013; 8: e74535.
  Article CAS PubMed PubMed Central Google Scholar
• Ruzankina Y, Pinzon-Guzman C, Asare A, Ong T, Pontano L, Cotsarelis G et al. Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss. Cell Stem Cell 2007; 1: 113–126.
  Article CAS PubMed PubMed Central Google Scholar
• Shan B, Xu J, Zhuo Y, Morris CA, Morris GF . Induction of p53-dependent activation of the human proliferating cell nuclear antigen gene in chromatin by ionizing radiation. J Biol Chem 2003; 278: 44009–44017.
  Article CAS PubMed Google Scholar
• Sharma GG, So S, Gupta A, Kumar R, Cayrou C, Avvakumov N et al. MOF and histone H4 acetylation at lysine 16 are critical for DNA damage response and double-strand break repair. Mol Cell Biol 2010; 30: 3582–3595.
  Article CAS PubMed PubMed Central Google Scholar
• Linard C, Gremy O, Benderitter M . Reduction of peroxisome proliferation-activated receptor gamma expression by gamma-irradiation as a mechanism contributing to inflammatory response in rat colon: modulation by the 5-aminosalicylic acid agonist. J Pharmacol Exp Ther 2008; 324: 911–920.
  Article CAS PubMed Google Scholar
• Arora H, Qureshi R, Park AK, Park WY . Coordinated regulation of ATF2 by miR-26b in gamma-irradiated lung cancer cells. PLoS ONE 2011; 6: e23802.
  Article CAS PubMed PubMed Central Google Scholar
• Imaeda M, Ishikawa H, Yoshida Y, Takahashi T, Ohkubo Y, Musha A et al. Long-term pathological and immunohistochemical features in the liver after intraoperative whole-liver irradiation in rats. J Radiat Res (e-pub ahead of print 23 February 2014; doi:10.1093/jrr/rru005).
  Article PubMed PubMed Central Google Scholar
• Das C, Lucia MS, Hansen KC, Tyler JK . CBP/p300-mediated acetylation of histone H3 on lysine 56. Nature 2009; 459: 113–117.
  Article CAS PubMed PubMed Central Google Scholar
• Alimova I, Birks DK, Harris PS, Knipstein JA, Venkataraman S, Marquez VE et al. Inhibition of EZH2 suppresses self-renewal and induces radiation sensitivity in atypical rhabdoid teratoid tumor cells. Neuro Oncol 2013; 15: 149–160.
  Article CAS PubMed Google Scholar
• Xu B, Chen H, Xu W, Zhang W, Buckley S, Zheng SG et al. Molecular mechanisms of MMP9 overexpression and its role in emphysema pathogenesis of Smad3-deficient mice. Am J Physiol Lung Cell Mol Physiol 2012; 303: L89–L96.
  Article CAS PubMed PubMed Central Google Scholar
• Kao GD, McKenna WG, Guenther MG, Muschel RJ, Lazar MA, Yen TJ . Histone deacetylase 4 interacts with 53BP1 to mediate the DNA damage response. J Cell Biol 2003; 160: 1017–1027.
  Article CAS PubMed PubMed Central Google Scholar
• Massague J . TGFbeta signalling in context. Nat Rev Mol Cell Biol 2012; 13: 616–630.
  Article CAS PubMed PubMed Central Google Scholar
• Wynn TA, Ramalingam TR . Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med 2012; 18: 1028–1040.
  Article CAS PubMed PubMed Central Google Scholar
• Ko YA, Mohtat D, Suzuki M, Park AS, Izquierdo MC, Han SY et al. Cytosine methylation changes in enhancer regions of core pro-fibrotic genes characterize kidney fibrosis development. Genome Biol 2013; 14: R108.
  Article PubMed PubMed Central Google Scholar
• Sandoval J, Heyn H, Moran S, Serra-Musach J, Pujana MA, Bibikova M et al. Validation of a DNA methylation microarray for 450000 CpG sites in the human genome. Epigenetics 2011; 6: 692–702.
  Article CAS PubMed Google Scholar
• Park PJ . ChIP-seq: advantages and challenges of a maturing technology. Nat Rev Genet 2009; 10: 669–680.
  Article CAS PubMed PubMed Central Google Scholar
• Mancuso M, Pazzaglia S, Tanori M, Hahn H, Merola P, Rebessi S et al. Basal cell carcinoma and its development: insights from radiation-induced tumors in Ptch1-deficient mice. Cancer Res 2004; 64: 934–941.
  Article CAS PubMed Google Scholar
• Mancuso M, Pasquali E, Leonardi S, Tanori M, Rebessi S, Di Majo V et al. Oncogenic bystander radiation effects in Patched heterozygous mouse cerebellum. Proc Natl Acad Sci USA 2008; 105: 12445–12450.
  Article CAS PubMed PubMed Central Google Scholar
• Wick W, Furnari FB, Naumann U, Cavenee WK, Weller M . PTEN gene transfer in human malignant glioma: sensitization to irradiation and CD95L-induced apoptosis. Oncogene 1999; 18: 3936–3943.
  Article CAS PubMed Google Scholar
• Zhang Y, Chen LH, Wang L, Wang HM, Zhang YW, Shi YS . Radiation-inducible PTEN expression radiosensitises hepatocellular carcinoma cells. Int J Radiat Biol 2010; 86: 964–974.
  Article CAS PubMed Google Scholar
• Sparfel L, Pinel-Marie ML, Boize M, Koscielny S, Desmots S, Pery A et al. Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci 2010; 114: 247–259.
  Article CAS PubMed Google Scholar
• Dees C, Schlottmann I, Funke R, Distler A, Palumbo-Zerr K, Zerr P et al. The Wnt antagonists DKK1 and SFRP1 are downregulated by promoter hypermethylation in systemic sclerosis. Ann Rheum Dis 2014; 73: 1232–1239.
  Article CAS PubMed Google Scholar
• Kim IG, Kim SY, Kim HA, Kim JY, Lee JH, Choi SI et al. Disturbance of DKK1 level is partly involved in survival of lung cancer cells via regulation of ROMO1 and gamma-radiation sensitivity. Biochem Biophys Res Commun 2013; 443: 49–55.
  Article PubMed CAS Google Scholar
• Shou J, Ali-Osman F, Multani AS, Pathak S, Fedi P, Srivenugopal KS . Human Dkk-1, a gene encoding a Wnt antagonist, responds to DNA damage and its overexpression sensitizes brain tumor cells to apoptosis following alkylation damage of DNA. Oncogene 2002; 21: 878–889.
  Article CAS PubMed Google Scholar
• Cisneros J, Hagood J, Checa M, Ortiz-Quintero B, Negreros M, Herrera I et al. Hypermethylation-mediated silencing of p14(ARF) in fibroblasts from idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2012; 303: L295–L303.
  Article CAS PubMed PubMed Central Google Scholar
• Khan S, Guevara C, Fujii G, Parry D . p14ARF is a component of the p53 response following ionizing irradiation of normal human fibroblasts. Oncogene 2004; 23: 6040–6046.
  Article CAS PubMed Google Scholar
• Simon M, Voss D, Park-Simon TW, Mahlberg R, Koster G . Role of p16 and p14ARF in radio- and chemosensitivity of malignant gliomas. Oncol Rep 2006; 16: 127–132.
  CAS PubMed Google Scholar
• Sanders YY, Pardo A, Selman M, Nuovo GJ, Tollefsbol TO, Siegal GP et al. Thy-1 promoter hypermethylation: a novel epigenetic pathogenic mechanism in pulmonary fibrosis. Am J Respir Cell Mol Biol 2008; 39: 610–618.
  Article CAS PubMed PubMed Central Google Scholar
• Zhang J, Yang Y, Wang Y, Zhang J, Wang Z, Yin M et al. Identification of hub genes related to the recovery phase of irradiation injury by microarray and integrated gene network analysis. PLoS ONE 2011; 6: e24680.
  Article CAS PubMed PubMed Central Google Scholar
• Wu CH, Tang SC, Wang PH, Lee H, Ko JL . Nickel-induced epithelial-mesenchymal transition by reactive oxygen species generation and E-cadherin promoter hypermethylation. J Biol Chem 2012; 287: 25292–25302.
  Article CAS PubMed PubMed Central Google Scholar
• Almeida C, Nagarajan D, Tian J, Leal SW, Wheeler K, Munley M et al. The role of alveolar epithelium in radiation-induced lung injury. PLoS ONE 2013; 8: e53628.
  Article CAS PubMed PubMed Central Google Scholar
• Shintani S, Hamakawa H, Nakashiro K, Shirota T, Hatori M, Tanaka M et al. Friend leukaemia insertion (Fli)-1 is a prediction marker candidate for radiotherapy resistant oral squamous cell carcinoma. Int J Oral Maxillofac Surg 2010; 39: 1115–1119.
  Article CAS PubMed Google Scholar
• Kis E, Szatmari T, Keszei M, Farkas R, Esik O, Lumniczky K et al. Microarray analysis of radiation response genes in primary human fibroblasts. Int J Radiat Oncol Biol Phys 2006; 66: 1506–1514.
  Article CAS PubMed Google Scholar
• Polistena A, Johnson LB, Rome A, Wittgren L, Back S, Osman N et al. Matrilysin expression related to radiation and microflora changes in murine bowel. J Surg Res 2011; 167: e137–e143.
  Article CAS PubMed Google Scholar
• Nadlonek NA, Weyant MJ, Yu JA, Cleveland JC Jr., Reece TB, Meng X et al. Radiation induces osteogenesis in human aortic valve interstitial cells. J Thorac Cardiovasc Surg 2012; 144: 1466–1470.
  Article CAS PubMed PubMed Central Google Scholar
• Hamama S, Gilbert-Sirieix M, Vozenin MC, Delanian S . Radiation-induced enteropathy: molecular basis of pentoxifylline-vitamin E anti-fibrotic effect involved TGF-beta1 cascade inhibition. Radiother Oncol 2012; 105: 305–312.
  Article CAS PubMed Google Scholar
• Abderrahmani R, Francois A, Buard V, Benderitter M, Sabourin JC, Crandall DL et al. Effects of pharmacological inhibition and genetic deficiency of plasminogen activator inhibitor-1 in radiation-induced intestinal injury. Int J Radiat Oncol Biol Phys 2009; 74: 942–948.
  Article CAS PubMed Google Scholar
• Rave-Frank M, Malik IA, Christiansen H, Naz N, Sultan S, Amanzada A et al. Rat model of fractionated (2Gy/day) 60Gy irradiation of the liver: long-term effects. Radiat Environ Biophys 2013; 52: 321–338.
  Article PubMed CAS Google Scholar
• Liu DG, Wang TM . Role of connective tissue growth factor in experimental radiation nephropathy in rats. Chin Med J (Engl) 2008; 121: 1925–1931.
  Article Google Scholar
• Ostrau C, Hulsenbeck J, Herzog M, Schad A, Torzewski M, Lackner KJ et al. Lovastatin attenuates ionizing radiation-induced normal tissue damage in vivo. Radiother Oncol 2009; 92: 492–499.
  Article CAS PubMed Google Scholar
• Ao X, Zhao L, Davis MA, Lubman DM, Lawrence TS, Kong FM . Radiation produces differential changes in cytokine profiles in radiation lung fibrosis sensitive and resistant mice. J Hematol Oncol 2009; 2: 6.
  Article PubMed PubMed Central CAS Google Scholar
• Moriconi F, Christiansen H, Raddatz D, Dudas J, Hermann RM, Rave-Frank M et al. Effect of radiation on gene expression of rat liver chemokines: in vivo and in vitro studies. Radiat Res 2008; 169: 162–169.
  Article CAS PubMed Google Scholar
• Malik IA, Moriconi F, Sheikh N, Naz N, Khan S, Dudas J et al. Single-dose gamma-irradiation induces up-regulation of chemokine gene expression and recruitment of granulocytes into the portal area but not into other regions of rat hepatic tissue. Am J Pathol 2010; 176: 1801–1815.
  Article CAS PubMed PubMed Central Google Scholar
• Balli D, Ustiyan V, Zhang Y, Wang IC, Masino AJ, Ren X et al. Foxm1 transcription factor is required for lung fibrosis and epithelial-to-mesenchymal transition. EMBO J 2013; 32: 231–244.
  Article CAS PubMed PubMed Central Google Scholar