- Wynn, T. A. & Ramalingam, T. R. Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat. Med. 18, 1028–1040 (2012).
CAS PubMed PubMed Central Google Scholar
- Lumeng, C. N. & Saltiel, A. R. Inflammatory links between obesity and metabolic disease. J. Clin. Invest. 121, 2111–2117 (2011).
CAS PubMed PubMed Central Google Scholar
- O’Neill, L. A. & Hardie, D. G. Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 493, 346–355 (2013).
PubMed Google Scholar
- Eltzschig, H. K. & Eckle, T. Ischemia and reperfusion—from mechanism to translation. Nat. Med. 17, 1391–1401 (2011).
CAS PubMed Google Scholar
- Hardie, D. G., Ross, F. A. & Hawley, S. A. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat. Rev. Mol. Cell Biol. 13, 251–262 (2012).
CAS PubMed PubMed Central Google Scholar
- Beers, M. F. & Morrisey, E. E. The three R’s of lung health and disease: repair, remodeling, and regeneration. J. Clin. Invest. 121, 2065–2073 (2011).
CAS PubMed PubMed Central Google Scholar
- Thannickal, V. J., Zhou, Y., Gaggar, A. & Duncan, S. R. Fibrosis: ultimate and proximate causes. J. Clin. Invest. 124, 4673–4677 (2014).
CAS PubMed PubMed Central Google Scholar
- Duffield, J. S., Lupher, M., Thannickal, V. J. & Wynn, T. A. Host responses in tissue repair and fibrosis. Annu. Rev. Pathol. 8, 241–276 (2013).
CAS PubMed Google Scholar
- Bueno, M. et al. PINK1 deficiency impairs mitochondrial homeostasis and promotes lung fibrosis. J. Clin. Invest. 125, 521–538 (2015).
PubMed Google Scholar
- Kobayashi, K. et al. Involvement of PARK2-mediated mitophagy in idiopathic pulmonary fibrosis pathogenesis. J. Immunol. 197, 504–516 (2016).
CAS PubMed Google Scholar
- Bernard, K. et al. Metabolic reprogramming is required for myofibroblast contractility and differentiation. J. Biol. Chem. 290, 25427–25438 (2015).
CAS PubMed PubMed Central Google Scholar
- Ramos, C. et al. Fibroblasts from idiopathic pulmonary fibrosis and normal lungs differ in growth rate, apoptosis, and tissue inhibitor of metalloproteinases expression. Am. J. Respir. Cell Mol. Biol. 24, 591–598 (2001).
CAS PubMed Google Scholar
- Romero, Y. et al. mTORC1 activation decreases autophagy in aging and idiopathic pulmonary fibrosis and contributes to apoptosis resistance in IPF fibroblasts. Aging Cell 15, 1103–1112 (2016).
CAS PubMed PubMed Central Google Scholar
- Ashley, S. L. et al. Targeting inhibitor of apoptosis proteins protects from bleomycin-induced lung fibrosis. Am. J. Respir. Cell Mol. Biol. 54, 482–492 (2016).
CAS PubMed PubMed Central Google Scholar
- Hecker, L. et al. Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance. Sci. Transl. Med. 6, 231ra247 (2014).
Google Scholar
- Inoki, K., Kim, J. & Guan, K. L. AMPK and mTOR in cellular energy homeostasis and drug targets. Annu. Rev. Pharmacol. Toxicol. 52, 381–400 (2012).
CAS PubMed Google Scholar
- Shaw, R. J. Metformin trims fats to restore insulin sensitivity. Nat. Med. 19, 1570–1572 (2013).
CAS PubMed Google Scholar
- Riera, C. E. & Dillin, A. Can aging be ‘drugged’? Nat. Med. 21, 1400–1405 (2015).
CAS PubMed Google Scholar
- Finkel, T. The metabolic regulation of aging. Nat. Med. 21, 1416–1423 (2015).
CAS PubMed Google Scholar
- Burkewitz, K., Zhang, Y. & Mair, W. B. AMPK at the nexus of energetics and aging. Cell Metab. 20, 10–25 (2014).
CAS PubMed PubMed Central Google Scholar
- Salminen, A. & Kaarniranta, K. AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res. Rev. 11, 230–241 (2012).
CAS PubMed Google Scholar
- Park, C. S. et al. Metformin reduces airway inflammation and remodeling via activation of AMP-activated protein kinase. Biochem. Pharmacol. 84, 1660–1670 (2012).
CAS PubMed Google Scholar
- Liu, Z. et al. AMP-activated protein kinase and glycogen synthase kinase 3β modulate the severity of sepsis-induced lung injury. Mol. Med. 21, 937–950 (2015).
CAS PubMed PubMed Central Google Scholar
- Sato, N. et al. Metformin attenuates lung fibrosis development via NOX4 suppression. Respir. Res. 17, 107 (2016).
PubMed PubMed Central Google Scholar
- Mishra, R. et al. AMP-activated protein kinase inhibits transforming growth factor-beta-induced Smad3-dependent transcription and myofibroblast transdifferentiation. J. Biol. Chem. 283, 10461–10469 (2008).
CAS PubMed Google Scholar
- Thakur, S. et al. Activation of AMP-activated protein kinase prevents TGF-β1-induced epithelial-mesenchymal transition and myofibroblast activation. Am. J. Pathol. 185, 2168–2180 (2015).
CAS PubMed PubMed Central Google Scholar
- Lim, J. Y., Oh, M. A., Kim, W. H., Sohn, H. Y. & Park, S. I. AMP-activated protein kinase inhibits TGF-β-induced fibrogenic responses of hepatic stellate cells by targeting transcriptional coactivator p300. J. Cell Physiol. 227, 1081–1089 (2012).
CAS PubMed Google Scholar
- Li, L. et al. Metformin attenuates gefitinib-induced exacerbation of pulmonary fibrosis by inhibition of TGF-β signaling pathway. Oncotarget 6, 43605–43619 (2015).
PubMed PubMed Central Google Scholar
- Park, I. H. et al. Metformin reduces TGF-β1-induced extracellular matrix production in nasal polyp-derived fibroblasts. Otolaryngol. Head Neck Surg. 150, 148–153 (2014).
PubMed Google Scholar
- Kottmann, R. M. et al. Lactic acid is elevated in idiopathic pulmonary fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-beta. Am. J. Respir. Crit. Care Med. 186, 740–751 (2012).
CAS PubMed PubMed Central Google Scholar
- Egan, D. F. et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331, 456–461 (2011).
CAS PubMed Google Scholar
- Parsons, M. J. & Green, D. R. Mitochondria in cell death. Essays Biochem. 47, 99–114 (2010).
CAS PubMed Google Scholar
- Tait, S. W. & Green, D. R. Mitochondria and cell death: outer membrane permeabilization and beyond. Nat. Rev. Mol. Cell Biol. 11, 621–632 (2010).
CAS PubMed Google Scholar
- Kim, J. W., Tchernyshyov, I., Semenza, G. L. & Dang, C. V. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 3, 177–185 (2006).
PubMed Google Scholar
- Spoden, G. A. et al. Pyruvate kinase isoenzyme M2 is a glycolytic sensor differentially regulating cell proliferation, cell size and apoptotic cell death dependent on glucose supply. Exp. Cell Res. 315, 2765–2774 (2009).
CAS PubMed Google Scholar
- Horowitz, J. C. et al. Activation of the pro-survival phosphatidylinositol 3-kinase/AKT pathway by transforming growth factor-β1 in mesenchymal cells is mediated by p38 MAPK-dependent induction of an autocrine growth factor. J. Biol. Chem. 279, 1359–1367 (2004).
CAS PubMed Google Scholar
- Foretz, M., Guigas, B., Bertrand, L., Pollak, M. & Viollet, B. Metformin: from mechanisms of action to therapies. Cell Metab. 20, 953–966 (2014).
CAS PubMed Google Scholar
- Knowler, W. C. et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med. 346, 393–403 (2002).
CAS PubMed Google Scholar
- Yu, G. et al. Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function. Nat. Med. 24, 39–49 (2018).
CAS PubMed Google Scholar
- Jiang, S. et al. Mitochondria and AMP-activated protein kinase-dependent mechanism of efferocytosis. J. Biol. Chem. 288, 26013–26026 (2013).
CAS PubMed PubMed Central Google Scholar
- Jian, M. Y., Alexeyev, M. F., Wolkowicz, P. E., Zmijewski, J. W. & Creighton, J. R. Metformin-stimulated AMPK-α1 promotes microvascular repair in acute lung injury. Am. J. Physiol. Lung Cell Mol. Physiol. 305, L844–855 (2013).
CAS PubMed PubMed Central Google Scholar
- Hecker, L. et al. NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury. Nat. Med. 15, 1077–1081 (2009).
CAS PubMed PubMed Central Google Scholar
- Jiang, S. et al. Human resistin promotes neutrophil proinflammatory activation and neutrophil extracellular trap formation and increases severity of acute lung injury. J. Immunol. 192, 4795–4803 (2014).
CAS PubMed Google Scholar
- Franco-Barraza, J., Beacham, D. A., Amatangelo, M. D., & Cukierman, E. Preparation of extracellular matrices produced by cultured and primary fibroblasts. Curr. Protoc. Cell Biol. 71, 10.9.1–10.9.34 (2016).
Google Scholar
- Hill, B. G. et al. Integration of cellular bioenergetics with mitochondrial quality control and autophagy. Biol. Chem. 393, 1485–1512 (2012).
CAS PubMed PubMed Central Google Scholar
- Graham, L. & Orenstein, J.M. Processing tissue and cells for transmission electron microscopy in diagnostic pathology and research. Nat. Protoc. 2, 2439–2450 (2007).
CAS PubMed PubMed Central Google Scholar