Latest progress on the molecular mechanisms of idiopathic pulmonary fibrosis (original) (raw)

References

1. Cottin V, Hirani NA, Hotchkin DL, Nambiar AM, Ogura T, Otaola M, Skowasch D, Park JS, Poonyagariyagorn HK, Wuyts W, Wells AU (2018) Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases. Eur Respir Rev. https://doi.org/10.1183/16000617.0076-2018
   Article PubMed Google Scholar
2. Karkkainen M, Nurmi H, Kettunen HP, Selander T, Purokivi M, Kaarteenaho R (2018) Underlying and immediate causes of death in patients with idiopathic pulmonary fibrosis. BMC Pulm Med 18:69. https://doi.org/10.1186/s12890-018-0642-4
   Article PubMed PubMed Central Google Scholar
3. Kropski JA, Blackwell TS (2019) Progress in understanding and treating idiopathic pulmonary fibrosis. Annu Rev Med 70:211–224. https://doi.org/10.1146/annurev-med-041317-102715
   Article CAS PubMed PubMed Central Google Scholar
4. Heukels P, Moor CC, von der Thusen JH, Wijsenbeek MS, Kool M (2019) Inflammation and immunity in IPF pathogenesis and treatment. Respir Med 147:79–91. https://doi.org/10.1016/j.rmed.2018.12.015
   Article CAS PubMed Google Scholar
5. Morikawa M, Derynck R, Miyazono K (2016) TGF-beta and the TGF-beta family: context-dependent roles in cell and tissue physiology. Cold Spring Harb Perspect Biol. https://doi.org/10.1101/cshperspect.a021873
   Article PubMed PubMed Central Google Scholar
6. Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH, Et A (1986) Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A 83:4167–4171. https://doi.org/10.1073/pnas.83.12.4167
   Article CAS PubMed PubMed Central Google Scholar
7. Kolahian S, Fernandez IE, Eickelberg O, Hartl D (2016) Immune mechanisms in pulmonary fibrosis. Am J Respir Cell Mol Biol 55:309–322. https://doi.org/10.1165/rcmb.2016-0121TR
   Article CAS PubMed Google Scholar
8. Massague J (1996) TGFbeta signaling: receptors, transducers, and Mad proteins. Cell 85:947–950. https://doi.org/10.1016/s0092-8674(00)81296-9
   Article CAS PubMed Google Scholar
9. Blobe GC, Schiemann WP, Lodish HF (2000) Role of transforming growth factor beta in human disease. N Engl J Med 342:1350–1358. https://doi.org/10.1056/NEJM200005043421807
   Article CAS PubMed Google Scholar
10. Shou J, Cao J, Zhang S, Sun R, Zhao M, Chen K, Su SB, Yang J, Yang T (2018) SIS3, a specific inhibitor of smad3, attenuates bleomycin-induced pulmonary fibrosis in mice. Biochem Biophys Res Commun 503:757–762. https://doi.org/10.1016/j.bbrc.2018.06.072
    Article CAS PubMed Google Scholar
11. Ryan RM, Mineo-Kuhn MM, Kramer CM, Finkelstein JN (1994) Growth factors alter neonatal type II alveolar epithelial cell proliferation. Am J Physiol 266:L17–L22. https://doi.org/10.1152/ajplung.1994.266.1.L17
    Article CAS PubMed Google Scholar
12. Mishra R, Cool BL, Laderoute KR, Foretz M, Viollet B, Simonson MS (2008) AMP-activated protein kinase inhibits transforming growth factor-beta-induced Smad3-dependent transcription and myofibroblast transdifferentiation. J Biol Chem 283:10461–10469. https://doi.org/10.1074/jbc.M800902200
    Article CAS PubMed Google Scholar
13. Rangarajan S, Bone NB, Zmijewska AA, Jiang S, Park DW, Bernard K, Locy ML, Ravi S, Deshane J, Mannon RB, Abraham E, Darley-Usmar V, Thannickal VJ, Zmijewski JW (2018) Metformin reverses established lung fibrosis in a bleomycin model. Nat Med 24:1121–1127. https://doi.org/10.1038/s41591-018-0087-6
    Article CAS PubMed PubMed Central Google Scholar
14. Mackinnon AC, Gibbons MA, Farnworth SL, Leffler H, Nilsson UJ, Delaine T, Simpson AJ, Forbes SJ, Hirani N, Gauldie J, Sethi T (2012) Regulation of transforming growth factor-beta1-driven lung fibrosis by galectin-3. Am J Respir Crit Care Med 185:537–546. https://doi.org/10.1164/rccm.201106-0965OC
    Article CAS PubMed PubMed Central Google Scholar
15. Hsu YA, Chang CY, Lan JL, Li JP, Lin HJ, Chen CS, Wan L, Liu FT (2020) Amelioration of bleomycin-induced pulmonary fibrosis via TGF-beta-induced Smad and non-Smad signaling pathways in galectin-9-deficient mice and fibroblast cells. J Biomed Sci 27:24. https://doi.org/10.1186/s12929-020-0616-8
    Article CAS PubMed PubMed Central Google Scholar
16. Bennett D, Bargagli E, Bianchi N, Landi C, Fossi A, Fui A, Sestini P, Refini RM, Rottoli P (2020) Elevated level of Galectin-1 in bronchoalveolar lavage of patients with idiopathic pulmonary fibrosis. Respir Physiol Neurobiol 273:103323. https://doi.org/10.1016/j.resp.2019.103323
    Article CAS PubMed Google Scholar
17. Liu YL, Chen BY, Nie J, Zhao GH, Zhuo JY, Yuan J, Li YC, Wang LL, Chen ZW (2020) Polydatin prevents bleomycin-induced pulmonary fibrosis by inhibiting the TGF-beta/Smad/ERK signaling pathway. Exp Ther Med 20:62. https://doi.org/10.3892/etm.2020.9190
    Article CAS PubMed PubMed Central Google Scholar
18. Kwon OS, Kim KT, Lee E, Kim M, Choi SH, Li H, Fornace AJ, Cho JH, Lee YS, Lee JS, Lee YJ, Cha HJ (2016) Induction of MiR-21 by stereotactic body radiotherapy contributes to the pulmonary fibrotic response. PLoS ONE 11:e154942. https://doi.org/10.1371/journal.pone.0154942
    Article CAS Google Scholar
19. Xiao X, Huang C, Zhao C, Gou X, Senavirathna LK, Hinsdale M, Lloyd P, Liu L (2015) Regulation of myofibroblast differentiation by miR-424 during epithelial-to-mesenchymal transition. Arch Biochem Biophys 566:49–57. https://doi.org/10.1016/j.abb.2014.12.007
    Article CAS PubMed Google Scholar
20. Huang C, Xiao X, Yang Y, Mishra A, Liang Y, Zeng X, Yang X, Xu D, Blackburn MR, Henke CA, Liu L (2019) Correction: microRNA-101 attenuates pulmonary fibrosis by inhibiting fibroblast proliferation and activation. J Biol Chem 294:6694. https://doi.org/10.1074/jbc.AAC119.008714
    Article PubMed PubMed Central Google Scholar
21. Zhang Y, Yao XH, Wu Y, Cao GK, Han D (2020) LncRNA NEAT1 regulates pulmonary fibrosis through miR-9-5p and TGF-beta signaling pathway. Eur Rev Med Pharmacol Sci 24:8483–8492. https://doi.org/10.26355/eurrev_202008_22661
    Article CAS PubMed Google Scholar
22. Liang C, Li X, Zhang L, Cui D, Quan X, Yang W (2015) The anti-fibrotic effects of microRNA-153 by targeting TGFBR-2 in pulmonary fibrosis. Exp Mol Pathol 99:279–285. https://doi.org/10.1016/j.yexmp.2015.07.011
    Article CAS PubMed Google Scholar
23. Zhang Q, Ye H, Xiang F, Song LJ, Zhou LL, Cai PC, Zhang JC, Yu F, Shi HZ, Su Y, Xin JB, Ma WL (2017) miR-18a-5p inhibits sub-pleural pulmonary fibrosis by targeting TGF-beta receptor II. Mol Ther 25:728–738. https://doi.org/10.1016/j.ymthe.2016.12.017
    Article CAS PubMed PubMed Central Google Scholar
24. Das S, Kumar M, Negi V, Pattnaik B, Prakash YS, Agrawal A, Ghosh B (2014) MicroRNA-326 regulates profibrotic functions of transforming growth factor-beta in pulmonary fibrosis. Am J Respir Cell Mol Biol 50:882–892. https://doi.org/10.1165/rcmb.2013-0195OC
    Article CAS PubMed PubMed Central Google Scholar
25. Graham JR, Williams CM, Yang Z (2014) MicroRNA-27b targets gremlin 1 to modulate fibrotic responses in pulmonary cells. J Cell Biochem 115:1539–1548. https://doi.org/10.1002/jcb.24809
    Article CAS PubMed Google Scholar
26. Zhang A, Wang H, Wang B, Yuan Y, Klein JD, Wang XH (2019) Exogenous miR-26a suppresses muscle wasting and renal fibrosis in obstructive kidney disease. FASEB J 33:13590–13601. https://doi.org/10.1096/fj.201900884R
    Article CAS PubMed PubMed Central Google Scholar
27. Jin SX, Wu QY, Yan WW, Ni CH (2017) Therapeutic effect of miR-489 in a mouse model of silica-induced matured pulmonary fibrosis. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 35:337–341. https://doi.org/10.3760/cma.j.issn.1001-9391.2017.05.004
    Article CAS PubMed Google Scholar
28. Lawrence J, Nho R (2018) The role of the mammalian target of rapamycin (mTOR) in pulmonary fibrosis. Int J Mol Sci. https://doi.org/10.3390/ijms19030778
    Article PubMed PubMed Central Google Scholar
29. Patel AS, Lin L, Geyer A, Haspel JA, An CH, Cao J, Rosas IO, Morse D (2012) Autophagy in idiopathic pulmonary fibrosis. PLoS ONE 7:e41394. https://doi.org/10.1371/journal.pone.0041394
    Article CAS PubMed PubMed Central Google Scholar
30. Mi S, Li Z, Yang HZ, Liu H, Wang JP, Ma YG, Wang XX, Liu HZ, Sun W, Hu ZW (2011) Blocking IL-17A promotes the resolution of pulmonary inflammation and fibrosis via TGF-beta1-dependent and -independent mechanisms. J Immunol 187:3003–3014. https://doi.org/10.4049/jimmunol.1004081
    Article CAS PubMed Google Scholar
31. Xie T, Xu Q, Wan H, Xing S, Shang C, Gao Y, He Z (2019) Lipopolysaccharide promotes lung fibroblast proliferation through autophagy inhibition via activation of the PI3K-Akt-mTOR pathway. Lab Investig 99:625–633. https://doi.org/10.1038/s41374-018-0160-2
    Article CAS PubMed Google Scholar
32. Lu Y, Azad N, Wang L, Iyer AK, Castranova V, Jiang BH, Rojanasakul Y (2010) Phosphatidylinositol-3-kinase/akt regulates bleomycin-induced fibroblast proliferation and collagen production. Am J Respir Cell Mol Biol 42:432–441. https://doi.org/10.1165/rcmb.2009-0002OC
    Article CAS PubMed Google Scholar
33. Gui YS, Wang L, Tian X, Li X, Ma A, Zhou W, Zeng N, Zhang J, Cai B, Zhang H, Chen JY, Xu KF (2015) mTOR overactivation and compromised autophagy in the pathogenesis of pulmonary fibrosis. PLoS ONE 10:e138625. https://doi.org/10.1371/journal.pone.0138625
    Article CAS Google Scholar
34. Gui X, Chen H, Cai H, Sun L, Gu L (2018) Leptin promotes pulmonary fibrosis development by inhibiting autophagy via PI3K/Akt/mTOR pathway. Biochem Biophys Res Commun 498:660–666. https://doi.org/10.1016/j.bbrc.2018.03.039
    Article CAS PubMed Google Scholar
35. Saxton RA, Sabatini DM (2017) mTOR signaling in growth, metabolism, and disease. Cell 168:960–976. https://doi.org/10.1016/j.cell.2017.02.004
    Article CAS PubMed PubMed Central Google Scholar
36. Huang J, Manning BD (2008) The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem J 412:179–190. https://doi.org/10.1042/BJ20080281
    Article CAS PubMed Google Scholar
37. Zinzalla V, Stracka D, Oppliger W, Hall MN (2011) Activation of mTORC2 by association with the ribosome. Cell 144:757–768. https://doi.org/10.1016/j.cell.2011.02.014
    Article CAS PubMed Google Scholar
38. Huang J, Manning BD (2009) A complex interplay between Akt, TSC2 and the two mTOR complexes. Biochem Soc Trans 37:217–222. https://doi.org/10.1042/BST0370217
    Article CAS PubMed PubMed Central Google Scholar
39. Yin W, Han J, Zhang Z, Han Z, Wang S (2018) Aloperine protects mice against bleomycin-induced pulmonary fibrosis by attenuating fibroblast proliferation and differentiation. Sci Rep 8:6265. https://doi.org/10.1038/s41598-018-24565-y
    Article CAS PubMed PubMed Central Google Scholar
40. Stracke ML, Krutzsch HC, Unsworth EJ, Arestad A, Cioce V, Schiffmann E, Liotta LA (1992) Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. J Biol Chem 267:2524–2529
    CAS PubMed Google Scholar
41. Ninou I, Magkrioti C, Aidinis V (2018) Autotaxin in pathophysiology and pulmonary fibrosis. Front Med (Lausanne) 5:180. https://doi.org/10.3389/fmed.2018.00180
    Article Google Scholar
42. Barbayianni E, Kaffe E, Aidinis V, Kokotos G (2015) Autotaxin, a secreted lysophospholipase D, as a promising therapeutic target in chronic inflammation and cancer. Prog Lipid Res 58:76–96. https://doi.org/10.1016/j.plipres.2015.02.001
    Article CAS PubMed Google Scholar
43. Oikonomou N, Mouratis MA, Tzouvelekis A, Kaffe E, Valavanis C, Vilaras G, Karameris A, Prestwich GD, Bouros D, Aidinis V (2012) Pulmonary autotaxin expression contributes to the pathogenesis of pulmonary fibrosis. Am J Respir Cell Mol Biol 47:566–574. https://doi.org/10.1165/rcmb.2012-0004OC
    Article CAS PubMed Google Scholar
44. Pradere JP, Klein J, Gres S, Guigne C, Neau E, Valet P, Calise D, Chun J, Bascands JL, Saulnier-Blache JS, Schanstra JP (2007) LPA1 receptor activation promotes renal interstitial fibrosis. J Am Soc Nephrol 18:3110–3118. https://doi.org/10.1681/ASN.2007020196
    Article CAS PubMed Google Scholar
45. Kaffe E, Katsifa A, Xylourgidis N, Ninou I, Zannikou M, Harokopos V, Foka P, Dimitriadis A, Evangelou K, Moulas AN, Georgopoulou U, Gorgoulis VG, Dalekos GN, Aidinis V (2017) Hepatocyte autotaxin expression promotes liver fibrosis and cancer. Hepatology 65:1369–1383. https://doi.org/10.1002/hep.28973
    Article CAS PubMed Google Scholar
46. Benesch MG, Ko YM, McMullen TP, Brindley DN (2014) Autotaxin in the crosshairs: taking aim at cancer and other inflammatory conditions. FEBS Lett 588:2712–2727. https://doi.org/10.1016/j.febslet.2014.02.009
    Article CAS PubMed Google Scholar
47. Badri L, Lama VN (2012) Lysophosphatidic acid induces migration of human lung-resident mesenchymal stem cells through the beta-catenin pathway. Stem Cells 30:2010–2019. https://doi.org/10.1002/stem.1171
    Article CAS PubMed PubMed Central Google Scholar
48. Cao P, Aoki Y, Badri L, Walker NM, Manning CM, Lagstein A, Fearon ER, Lama VN (2017) Autocrine lysophosphatidic acid signaling activates beta-catenin and promotes lung allograft fibrosis. J Clin Investig 127:1517–1530. https://doi.org/10.1172/JCI88896
    Article PubMed PubMed Central Google Scholar
49. Huang LS, Fu P, Patel P, Harijith A, Sun T, Zhao Y, Garcia JG, Chun J, Natarajan V (2013) Lysophosphatidic acid receptor-2 deficiency confers protection against bleomycin-induced lung injury and fibrosis in mice. Am J Respir Cell Mol Biol 49:912–922. https://doi.org/10.1165/rcmb.2013-0070OC
    Article CAS PubMed PubMed Central Google Scholar
50. Gierse J, Thorarensen A, Beltey K, Bradshaw-Pierce E, Cortes-Burgos L, Hall T, Johnston A, Murphy M, Nemirovskiy O, Ogawa S, Pegg L, Pelc M, Prinsen M, Schnute M, Wendling J, Wene S, Weinberg R, Wittwer A, Zweifel B, Masferrer J (2010) A novel autotaxin inhibitor reduces lysophosphatidic acid levels in plasma and the site of inflammation. J Pharmacol Exp Ther 334:310–317. https://doi.org/10.1124/jpet.110.165845
    Article CAS PubMed Google Scholar
51. Cortinovis M, Aiello S, Mister M, Conde-Knape K, Noris M, Novelli R, Solini S, Rodriguez OP, Benigni A, Remuzzi G (2020) Autotaxin inhibitor protects from chronic allograft injury in rat kidney allotransplantation. Nephron 144:38–48. https://doi.org/10.1159/000502908
    Article CAS PubMed Google Scholar
52. Nikolaou A, Ninou I, Kokotou MG, Kaffe E, Afantitis A, Aidinis V, Kokotos G (2018) Hydroxamic acids constitute a novel class of autotaxin inhibitors that exhibit in vivo efficacy in a pulmonary fibrosis model. J Med Chem 61:3697–3711. https://doi.org/10.1021/acs.jmedchem.8b00232
    Article CAS PubMed Google Scholar
53. Desroy N, Housseman C, Bock X, Joncour A, Bienvenu N, Cherel L, Labeguere V, Rondet E, Peixoto C, Grassot JM, Picolet O, Annoot D, Triballeau N, Monjardet A, Wakselman E, Roncoroni V, Le Tallec S, Blanque R, Cottereaux C, Vandervoort N, Christophe T, Mollat P, Lamers M, Auberval M, Hrvacic B, Ralic J, Oste L, van der Aar E, Brys R, Heckmann B (2017) Discovery of 2-[[2-ethyl-6-[4-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]piperazin-1-yl]-8-methyli midazo[1,2-a]pyridin-3-yl]methylamino]-4-(4-fluorophenyl)thiazole-5-carbonitrile (GLPG1690), a first-in-class autotaxin inhibitor undergoing clinical evaluation for the treatment of idiopathic pulmonary fibrosis. J Med Chem 60:3580–3590. https://doi.org/10.1021/acs.jmedchem.7b00032
    Article CAS PubMed Google Scholar
54. van der Aar E, Desrivot J, Dupont S, Heckmann B, Fieuw A, Stutvoet S, Fagard L, Van de Wal K, Helmer E (2019) Safety, pharmacokinetics, and pharmacodynamics of the autotaxin inhibitor GLPG1690 in healthy subjects: Phase 1 randomized trials. J Clin Pharmacol 59:1366–1378. https://doi.org/10.1002/jcph.1424
    Article CAS PubMed PubMed Central Google Scholar
55. Konigshoff M, Balsara N, Pfaff EM, Kramer M, Chrobak I, Seeger W, Eickelberg O (2008) Functional Wnt signaling is increased in idiopathic pulmonary fibrosis. PLoS ONE 3:e2142. https://doi.org/10.1371/journal.pone.0002142
    Article CAS PubMed PubMed Central Google Scholar
56. Skronska-Wasek W, Gosens R, Konigshoff M, Baarsma HA (2018) WNT receptor signalling in lung physiology and pathology. Pharmacol Ther 187:150–166. https://doi.org/10.1016/j.pharmthera.2018.02.009
    Article CAS PubMed Google Scholar
57. Vuga LJ, Ben-Yehudah A, Kovkarova-Naumovski E, Oriss T, Gibson KF, Feghali-Bostwick C, Kaminski N (2009) WNT5A is a regulator of fibroblast proliferation and resistance to apoptosis. Am J Respir Cell Mol Biol 41:583–589. https://doi.org/10.1165/rcmb.2008-0201OC
    Article CAS PubMed PubMed Central Google Scholar
58. Cao H, Wang C, Chen X, Hou J, Xiang Z, Shen Y, Han X (2018) Inhibition of Wnt/beta-catenin signaling suppresses myofibroblast differentiation of lung resident mesenchymal stem cells and pulmonary fibrosis. Sci Rep 8:13644. https://doi.org/10.1038/s41598-018-28968-9
    Article CAS PubMed PubMed Central Google Scholar
59. Xu L, Cui WH, Zhou WC, Li DL, Li LC, Zhao P, Mo XT, Zhang Z, Gao J (2017) Activation of Wnt/beta-catenin signalling is required for TGF-beta/Smad2/3 signalling during myofibroblast proliferation. J Cell Mol Med 21:1545–1554. https://doi.org/10.1111/jcmm.13085
    Article CAS PubMed PubMed Central Google Scholar
60. Sennello JA, Misharin AV, Flozak AS, Berdnikovs S, Cheresh P, Varga J, Kamp DW, Budinger GR, Gottardi CJ, Lam AP (2017) Lrp5/beta-catenin signaling controls lung macrophage differentiation and inhibits resolution of fibrosis. Am J Respir Cell Mol Biol 56:191–201. https://doi.org/10.1165/rcmb.2016-0147OC
    Article CAS PubMed PubMed Central Google Scholar
61. Acebron SP, Karaulanov E, Berger BS, Huang YL, Niehrs C (2014) Mitotic wnt signaling promotes protein stabilization and regulates cell size. Mol Cell 54:663–674. https://doi.org/10.1016/j.molcel.2014.04.014
    Article CAS PubMed Google Scholar
62. Chen X, Shi C, Cao H, Chen L, Hou J, Xiang Z, Hu K, Han X (2018) The hedgehog and Wnt/beta-catenin system machinery mediate myofibroblast differentiation of LR-MSCs in pulmonary fibrogenesis. Cell Death Dis 9:639. https://doi.org/10.1038/s41419-018-0692-9
    Article CAS PubMed PubMed Central Google Scholar
63. Aumiller V, Balsara N, Wilhelm J, Gunther A, Konigshoff M (2013) WNT/beta-catenin signaling induces IL-1beta expression by alveolar epithelial cells in pulmonary fibrosis. Am J Respir Cell Mol Biol 49:96–104. https://doi.org/10.1165/rcmb.2012-0524OC
    Article CAS PubMed Google Scholar
64. Tanjore H, Degryse AL, Crossno PF, Xu XC, McConaha ME, Jones BR, Polosukhin VV, Bryant AJ, Cheng DS, Newcomb DC, McMahon FB, Gleaves LA, Blackwell TS, Lawson WE (2013) Beta-catenin in the alveolar epithelium protects from lung fibrosis after intratracheal bleomycin. Am J Respir Crit Care Med 187:630–639. https://doi.org/10.1164/rccm.201205-0972OC
    Article CAS PubMed PubMed Central Google Scholar
65. Konigshoff M, Kramer M, Balsara N, Wilhelm J, Amarie OV, Jahn A, Rose F, Fink L, Seeger W, Schaefer L, Gunther A, Eickelberg O (2009) WNT1-inducible signaling protein-1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis. J Clin Investig 119:772–787. https://doi.org/10.1172/JCI33950
    Article CAS PubMed PubMed Central Google Scholar
66. Henderson WJ, Chi EY, Ye X, Nguyen C, Tien YT, Zhou B, Borok Z, Knight DA, Kahn M (2010) Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis. Proc Natl Acad Sci U S A 107:14309–14314. https://doi.org/10.1073/pnas.1001520107
    Article PubMed PubMed Central Google Scholar
67. Boyapally R, Pulivendala G, Bale S, Godugu C (2019) Niclosamide alleviates pulmonary fibrosis in vitro and in vivo by attenuation of epithelial-to-mesenchymal transition, matrix proteins and Wnt/beta-catenin signaling: a drug repurposing study. Life Sci 220:8–20. https://doi.org/10.1016/j.lfs.2018.12.061
    Article CAS PubMed Google Scholar
68. Hosseinzadeh A, Javad-Moosavi SA, Reiter RJ, Hemati K, Ghaznavi H, Mehrzadi S (2018) Idiopathic pulmonary fibrosis (IPF) signaling pathways and protective roles of melatonin. Life Sci 201:17–29. https://doi.org/10.1016/j.lfs.2018.03.032
    Article CAS PubMed Google Scholar
69. Kiyokawa H, Morimoto M (2020) Notch signaling in the mammalian respiratory system, specifically the trachea and lungs, in development, homeostasis, regeneration, and disease. Dev Growth Differ 62:67–79. https://doi.org/10.1111/dgd.12628
    Article PubMed Google Scholar
70. Vaughan AE, Brumwell AN, Xi Y, Gotts JE, Brownfield DG, Treutlein B, Tan K, Tan V, Liu FC, Looney MR, Matthay MA, Rock JR, Chapman HA (2015) Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury. Nature 517:621–625. https://doi.org/10.1038/nature14112
    Article CAS PubMed Google Scholar
71. Li X, Zhang X, Leathers R, Makino A, Huang C, Parsa P, Macias J, Yuan JX, Jamieson SW, Thistlethwaite PA (2009) Notch3 signaling promotes the development of pulmonary arterial hypertension. Nat Med 15:1289–1297. https://doi.org/10.1038/nm.2021
    Article CAS PubMed PubMed Central Google Scholar
72. Xing Y, Li A, Borok Z, Li C, Minoo P (2012) NOTCH1 is required for regeneration of Clara cells during repair of airway injury. Stem Cells 30:946–955. https://doi.org/10.1002/stem.1059
    Article CAS PubMed PubMed Central Google Scholar
73. Ono Y, Sensui H, Okutsu S, Nagatomi R (2007) Notch2 negatively regulates myofibroblastic differentiation of myoblasts. J Cell Physiol 210:358–369. https://doi.org/10.1002/jcp.20838
    Article CAS PubMed Google Scholar
74. Xu K, Nieuwenhuis E, Cohen BL, Wang W, Canty AJ, Danska JS, Coultas L, Rossant J, Wu MY, Piscione TD, Nagy A, Gossler A, Hicks GG, Hui CC, Henkelman RM, Yu LX, Sled JG, Gridley T, Egan SE (2010) Lunatic Fringe-mediated Notch signaling is required for lung alveogenesis. Am J Physiol Lung Cell Mol Physiol 298:L45–L56. https://doi.org/10.1152/ajplung.90550.2008
    Article CAS PubMed Google Scholar
75. Aoyagi-Ikeda K, Maeno T, Matsui H, Ueno M, Hara K, Aoki Y, Aoki F, Shimizu T, Doi H, Kawai-Kowase K, Iso T, Suga T, Arai M, Kurabayashi M (2011) Notch induces myofibroblast differentiation of alveolar epithelial cells via transforming growth factor-{beta}-Smad3 pathway. Am J Respir Cell Mol Biol 45:136–144. https://doi.org/10.1165/rcmb.2010-0140oc
    Article CAS PubMed Google Scholar
76. Eliasz S, Liang S, Chen Y, De Marco MA, Machek O, Skucha S, Miele L, Bocchetta M (2010) Notch-1 stimulates survival of lung adenocarcinoma cells during hypoxia by activating the IGF-1R pathway. Oncogene 29:2488–2498. https://doi.org/10.1038/onc.2010.7
    Article CAS PubMed PubMed Central Google Scholar
77. Cao Z, Lis R, Ginsberg M, Chavez D, Shido K, Rabbany SY, Fong GH, Sakmar TP, Rafii S, Ding BS (2016) Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis. Nat Med 22:154–162. https://doi.org/10.1038/nm.4035
    Article CAS PubMed PubMed Central Google Scholar
78. Chu H, Shi Y, Jiang S, Zhong Q, Zhao Y, Liu Q, Ma Y, Shi X, Ding W, Zhou X, Cui J, Jin L, Guo G, Wang J (2017) Treatment effects of the traditional Chinese medicine Shenks in bleomycin-induced lung fibrosis through regulation of TGF-beta/Smad3 signaling and oxidative stress. Sci Rep 7:2252. https://doi.org/10.1038/s41598-017-02293-z
    Article CAS PubMed PubMed Central Google Scholar
79. Grosche J, Meissner J, Eble JA (2018) More than a syllable in fib-ROS-is: the role of ROS on the fibrotic extracellular matrix and on cellular contacts. Mol Asp Med 63:30–46. https://doi.org/10.1016/j.mam.2018.03.005
    Article CAS Google Scholar
80. Bernard K, Logsdon NJ, Miguel V, Benavides GA, Zhang J, Carter AB, Darley-Usmar VM, Thannickal VJ (2017) NADPH oxidase 4 (Nox4) suppresses mitochondrial biogenesis and bioenergetics in lung fibroblasts via a nuclear factor erythroid-derived 2-like 2 (Nrf2)-dependent pathway. J Biol Chem 292:3029–3038. https://doi.org/10.1074/jbc.M116.752261
    Article CAS PubMed PubMed Central Google Scholar
81. Anathy V, Lahue KG, Chapman DG, Chia SB, Casey DT, Aboushousha R, van der Velden J, Elko E, Hoffman SM, McMillan DH, Jones JT, Nolin JD, Abdalla S, Schneider R, Seward DJ, Roberson EC, Liptak MD, Cousins ME, Butnor KJ, Taatjes DJ, Budd RC, Irvin CG, Ho YS, Hakem R, Brown KK, Matsui R, Bachschmid MM, Gomez JL, Kaminski N, van der Vliet A, Janssen-Heininger Y (2018) Reducing protein oxidation reverses lung fibrosis. Nat Med 24:1128–1135. https://doi.org/10.1038/s41591-018-0090-y
    Article CAS PubMed PubMed Central Google Scholar
82. Kang YP, Lee SB, Lee JM, Kim HM, Hong JY, Lee WJ, Choi CW, Shin HK, Kim DJ, Koh ES, Park CS, Kwon SW, Park SW (2016) Metabolic profiling regarding pathogenesis of idiopathic pulmonary fibrosis. J Proteome Res 15:1717–1724. https://doi.org/10.1021/acs.jproteome.6b00156
    Article CAS PubMed Google Scholar
83. Li L, Cai L, Zheng L, Hu Y, Yuan W, Guo Z, Li W (2018) Gefitinib inhibits bleomycin-induced pulmonary fibrosis via alleviating the oxidative damage in mice. Oxid Med Cell Longev 2018:8249693. https://doi.org/10.1155/2018/8249693
    Article CAS PubMed PubMed Central Google Scholar
84. Kim SJ, Cheresh P, Jablonski RP, Morales-Nebreda L, Cheng Y, Hogan E, Yeldandi A, Chi M, Piseaux R, Ridge K, Michael HC, Chandel N, Scott BG, Kamp DW (2016) Mitochondrial catalase overexpressed transgenic mice are protected against lung fibrosis in part via preventing alveolar epithelial cell mitochondrial DNA damage. Free Radic Biol Med 101:482–490. https://doi.org/10.1016/j.freeradbiomed.2016.11.007
    Article CAS PubMed PubMed Central Google Scholar
85. Reddy NM, Kleeberger SR, Cho HY, Yamamoto M, Kensler TW, Biswal S, Reddy SP (2007) Deficiency in Nrf2-GSH signaling impairs type II cell growth and enhances sensitivity to oxidants. Am J Respir Cell Mol Biol 37:3–8. https://doi.org/10.1165/rcmb.2007-0004RC
    Article CAS PubMed PubMed Central Google Scholar
86. Jablonski RP, Kim SJ, Cheresh P, Williams DB, Morales-Nebreda L, Cheng Y, Yeldandi A, Bhorade S, Pardo A, Selman M, Ridge K, Gius D, Budinger G, Kamp DW (2017) SIRT3 deficiency promotes lung fibrosis by augmenting alveolar epithelial cell mitochondrial DNA damage and apoptosis. FASEB J 31:2520–2532. https://doi.org/10.1096/fj.201601077R
    Article CAS PubMed PubMed Central Google Scholar
87. Sundaresan NR, Bindu S, Pillai VB, Samant S, Pan Y, Huang JY, Gupta M, Nagalingam RS, Wolfgeher D, Verdin E, Gupta MP (2015) SIRT3 blocks aging-associated tissue fibrosis in mice by deacetylating and activating glycogen synthase kinase 3beta. Mol Cell Biol 36:678–692. https://doi.org/10.1128/MCB.00586-15
    Article CAS PubMed Google Scholar
88. Larson-Casey JL, He C, Carter AB (2020) Mitochondrial quality control in pulmonary fibrosis. Redox Biol 33:101426. https://doi.org/10.1016/j.redox.2020.101426
    Article CAS PubMed PubMed Central Google Scholar
89. Hecker L, Vittal R, Jones T, Jagirdar R, Luckhardt TR, Horowitz JC, Pennathur S, Martinez FJ, Thannickal VJ (2009) NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury. Nat Med 15:1077–1081. https://doi.org/10.1038/nm.2005
    Article CAS PubMed PubMed Central Google Scholar
90. Jarman ER, Khambata VS, Cope C, Jones P, Roger J, Ye LY, Duggan N, Head D, Pearce A, Press NJ, Bellenie B, Sohal B, Jarai G (2014) An inhibitor of NADPH oxidase-4 attenuates established pulmonary fibrosis in a rodent disease model. Am J Respir Cell Mol Biol 50:158–169. https://doi.org/10.1165/rcmb.2013-0174OC
    Article CAS PubMed Google Scholar
91. Sato N, Takasaka N, Yoshida M, Tsubouchi K, Minagawa S, Araya J, Saito N, Fujita Y, Kurita Y, Kobayashi K, Ito S, Hara H, Kadota T, Yanagisawa H, Hashimoto M, Utsumi H, Wakui H, Kojima J, Numata T, Kaneko Y, Odaka M, Morikawa T, Nakayama K, Kohrogi H, Kuwano K (2016) Metformin attenuates lung fibrosis development via NOX4 suppression. Respir Res 17:107. https://doi.org/10.1186/s12931-016-0420-x
    Article CAS PubMed PubMed Central Google Scholar
92. Augsburger F, Filippova A, Rasti D, Seredenina T, Lam M, Maghzal G, Mahiout Z, Jansen-Durr P, Knaus UG, Doroshow J, Stocker R, Krause KH, Jaquet V (2019) Pharmacological characterization of the seven human NOX isoforms and their inhibitors. Redox Biol 26:101272. https://doi.org/10.1016/j.redox.2019.101272
    Article CAS PubMed PubMed Central Google Scholar

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