AMPK orchestrates an elaborate cascade protecting tissue from fibrosis and aging

Ageing Research Reviews

Volumn 38, Issue , 2017, Pages 18-27

  Jiang, Shuai ^a,b   Li, Tian ^b   Yang, Zhi ^b   Yi, Wei ^c   Di, Shouyin ^d   Sun, Yang ^c   Wang, Dongjin ^e   Yang, Yang ^a,b  

^a NORTHWEST UNIVERSITY   (China)

^b FOURTH MILITARY MEDICAL UNIVERSITY   (China)

^c FOURTH MILITARY MEDICAL UNIVERSITY   (China)

^d FOURTH MILITARY MEDICAL UNIVERSITY   (China)

^e THE AFFILIATED DRUM TOWER HOSPITAL OF NANJING UNIVERSITY MEDICAL SCHOOL   (China)

Author keywords

Aging; AMP activated protein kinase; Excessive extracellular matrix; Fibrogenesis; Fibrosis; Inflammation

Indexed keywords

HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE;

AGING; FIBROGENESIS; FIBROSIS; HEART MUSCLE FIBROSIS; HUMAN; KIDNEY FIBROSIS; LIVER FIBROSIS; LUNG FIBROSIS; NONHUMAN; PROTEIN FUNCTION; REGULATORY MECHANISM; REVIEW; ANIMAL; CARDIAC MUSCLE; ENZYMOLOGY; EXTRACELLULAR MATRIX; KIDNEY; LIVER; LUNG; METABOLISM; PHYSIOLOGY;

AGING; AMP-ACTIVATED PROTEIN KINASES; ANIMALS; EXTRACELLULAR MATRIX; FIBROSIS; HUMANS; KIDNEY; LIVER; LUNG; MYOCARDIUM;

EID: 85024476156     PISSN: 15681637     EISSN: 18729649     Source Type: Journal    
DOI: 10.1016/j.arr.2017.07.001     Document Type: Review

References (94)

1. Arad, M., Moskowitz, I.P., Patel, V.V., Ahmad, F., Perez-Atayde, A.R., Sawyer, D.B., Walter, M., Li, G.H., Burgon, P.G., Maguire, C.T., Stapleton, D., Schmitt, J.P., Guo, X.X., Pizard, A., Kupershmidt, S., Roden, D.M., Berul, C.I., Seidman, C.E., Seidman, J.G., Transgenic mice overexpressing mutant PRKAG2 define the cause of Wolff-Parkinson-White syndrome in glycogen storage cardiomyopathy. Circulation 107:22 (2003), 2850–2856.
2. Armanios, M., Telomerase mutations and the pulmonary fibrosis-bone marrow failure syndrome complex. N. Engl. J. Med., 367(4), 2012, 384 (author reply 384).
3. Birbrair, A., Zhang, T., Files, D.C., Mannava, S., Smith, T., Wang, Z.M., Messi, M.L., Mintz, A., Delbono, O., Type-1 pericytes accumulate after tissue injury and produce collagen in an organ-dependent manner. Stem Cell Res. Ther., 5(6), 2014, 122.
4. Cao, T., Gao, Z., Gu, L., Chen, M., Yang, B., Cao, K., Huang, H., Li, M., AdipoR1/APPL1 potentiates the protective effects of globular adiponectin on angiotensin II-induced cardiac hypertrophy and fibrosis in neonatal rat atrial myocytes and fibroblasts. PLoS One, 9(8), 2014, e103793.
5. Carling, D., Viollet, B., Beyond energy homeostasis: the expanding role of AMP-activated protein kinase in regulating metabolism. Cell Metab. 21:6 (2015), 799–804.
6. Carling, D., Aguan, K., Woods, A., Verhoeven, A.J., Beri, R.K., Brennan, C.H., Sidebottom, C., Davison, M.D., Scott, J., Mammalian AMP-activated protein kinase is homologous to yeast and plant protein kinases involved in the regulation of carbon metabolism. J. Biol. Chem. 269:15 (1994), 11442–11448.
7. Cavaglieri, R.C., Day, R.T., Feliers, D., Abboud, H.E., Metformin prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction. Mol. Cell. Endocrinol. 412 (2015), 116–122.
8. Chen, K.H., Hsu, H.H., Lee, C.C., Yen, T.H., Ko, Y.C., Yang, C.W., Hung, C.C., The AMPK agonist AICAR inhibits TGF-beta1 induced activation of kidney myofibroblasts. PLoS One, 9(9), 2014, e106554.
9. Cho, Y.R., Lim, J.H., Kim, M.Y., Kim, T.W., Hong, B.Y., Kim, Y.S., Chang, Y.S., Kim, H.W., Park, C.W., Therapeutic effects of fenofibrate on diabetic peripheral neuropathy by improving endothelial and neural survival in db/db mice. PLoS One, 9(1), 2014, e83204.
10. Cieslik, K.A., Taffet, G.E., Crawford, J.R., Trial, J., Mejia Osuna, P., Entman, M.L., AICAR-dependent AMPK activation improves scar formation in the aged heart in a murine model of reperfused myocardial infarction. J. Mol. Cell. Cardiol. 63 (2013), 26–36.
11. Daskalopoulos, E.P., Dufeys, C., Bertrand, L., Beauloye, C., Horman, S., AMPK in cardiac fibrosis and repair: actions beyond metabolic regulation. J. Mol. Cell. Cardiol. 91 (2016), 188–200.
12. Dirks, A.J., Hofer, T., Marzetti, E., Pahor, M., Leeuwenburgh, C., Mitochondrial DNA mutations, energy metabolism and apoptosis in aging muscle. Ageing Res. Rev. 5:2 (2006), 179–195.
13. Elborn, J.S., Cystic Fibrosis. 2016, Lancet.
14. Friis, R.M., Glaves, J.P., Huan, T., Li, L., Sykes, B.D., Schultz, M.C., Rewiring AMPK and mitochondrial retrograde signaling for metabolic control of aging and histone acetylation in respiratory-defective cells. Cell Rep. 7:2 (2014), 565–574.
15. Gulati, A., Jabbour, A., Ismail, T.F., Guha, K., Khwaja, J., Raza, S., Morarji, K., Brown, T.D., Ismail, N.A., Dweck, M.R., Di Pietro, E., Roughton, M., Wage, R., Daryani, Y., O'Hanlon, R., Sheppard, M.N., Alpendurada, F., Lyon, A.R., Cook, S.A., Cowie, M.R., Assomull, R.G., Pennell, D.J., Prasad, S.K., Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. JAMA 309:9 (2013), 896–908.
16. Hallows, K.R., Raghuram, V., Kemp, B.E., Witters, L.A., Foskett, J.K., Inhibition of cystic fibrosis transmembrane conductance regulator by novel interaction with the metabolic sensor AMP-activated protein kinase. J. Clin. Invest. 105:12 (2000), 1711–1721.
17. Hallows, K.R., McCane, J.E., Kemp, B.E., Witters, L.A., Foskett, J.K., Regulation of channel gating by AMP-activated protein kinase modulates cystic fibrosis transmembrane conductance regulator activity in lung submucosal cells. J. Biol. Chem. 278:2 (2003), 998–1004.
18. Hallows, K.R., Fitch, A.C., Richardson, C.A., Reynolds, P.R., Clancy, J.P., Dagher, P.C., Witters, L.A., Kolls, J.K., Pilewski, J.M., Up-regulation of AMP-activated kinase by dysfunctional cystic fibrosis transmembrane conductance regulator in cystic fibrosis airway epithelial cells mitigates excessive inflammation. J. Biol. Chem. 281:7 (2006), 4231–4241.
19. Hardman, S.E., Hall, D.E., Cabrera, A.J., Hancock, C.R., Thomson, D.M., The effects of age and muscle contraction on AMPK activity and heterotrimer composition. Exp. Gerontol. 55 (2014), 120–128.
20. Heinrichs, D., Berres, M.L., Coeuru, M., Knauel, M., Nellen, A., Fischer, P., Philippeit, C., Bucala, R., Trautwein, C., Wasmuth, H.E., Bernhagen, J., Protective role of macrophage migration inhibitory factor in nonalcoholic steatohepatitis. FASEB J. 28:12 (2014), 5136–5147.
21. Hermida, N., Markl, A., Hamelet, J., Van Assche, T., Vanderper, A., Herijgers, P., van Bilsen, M., Hilfiker-Kleiner, D., Noppe, G., Beauloye, C., Horman, S., Balligand, J.L., HMGCoA reductase inhibition reverses myocardial fibrosis and diastolic dysfunction through AMP-activated protein kinase activation in a mouse model of metabolic syndrome. Cardiovasc. Res. 99:1 (2013), 44–54.
22. Hong-Brown, L.Q., Brown, C.R., Navaratnarajah, M., Lang, C.H., Adamts1 mediates ethanol-induced alterations in collagen and elastin via a FoxO1-sestrin3-AMPK signaling cascade in myocytes. J. Cell. Biochem. 116:1 (2015), 91–101.
23. Hu, W., Ma, Z., Jiang, S., Fan, C., Deng, C., Yan, X., Di, S., Lv, J., Reiter, R.J., Yang, Y., Melatonin: the dawning of a treatment for fibrosis?. J. Pineal Res. 60:2 (2016), 121–131.
24. Iwata, T., Yoshida, S., Nagato, K., Nakajima, T., Suzuki, H., Tagawa, T., Mizobuchi, T., Ota, S., Nakatani, Y., Yoshino, I., Experience with perioperative pirfenidone for lung cancer surgery in patients with idiopathic pulmonary fibrosis. Surg. Today 45:10 (2015), 1263–1270.
25. Jackaman, C., Tomay, F., Duong, L., Abdol Razak, N.B., Pixley, F.J., Metharom, P., Nelson, D.J., Aging and cancer: the role of macrophages and neutrophils. Ageing Res. Rev. 36 (2017), 105–116.
26. Jenkins, G., Goodwin, A., Novel approaches to pulmonary fibrosis. Clin. Med. (Lond.) 14:Suppl. 6 (2014), s45–49.
27. Jiang, S., Tian, S., Wu, X., Tao, Y., Jiang, D., Effect of AMP-activated protein kinase activation on cardiac fibroblast proliferation induced by coxsackievirus B3. Exp. Ther. Med. 11:6 (2016), 2547–2552.
28. Jiang, S., Yang, Y., Li, T., Ma, Z., Hu, W., Deng, C., Fan, C., Lv, J., Sun, Y., Yi, W., An overview of the mechanisms and novel roles of Nrf2 in cardiovascular diseases. Expert Opin. Ther. Targets 20:12 (2016), 1413–1424.
29. Jin, Y., Bai, Y., Ni, H., Qiang, L., Ye, L., Shan, Y., Zhou, M., Activation of autophagy through calcium-dependent AMPK/mTOR and PKCtheta pathway causes activation of rat hepatic stellate cells under hypoxic stress. FEBS Lett. 590:5 (2016), 672–682.
30. Jo, H.K., Kim, G.W., Jeong, K.J., Kim, D.Y., Chung, S.H., Eugenol ameliorates hepatic steatosis and fibrosis by down-regulating SREBP1 gene expression via AMPK-mTOR-p70S6 K signaling pathway. Biol. Pharm. Bull. 37:8 (2014), 1341–1351.
31. Ju, K.D., Kim, H.J., Tsogbadrakh, B., Lee, J., Ryu, H., Cho, E.J., Hwang, Y.H., Kim, K., Yang, J., Ahn, C., Oh, K.H., HL156A, a novel AMP-activated protein kinase activator, is protective against peritoneal fibrosis in an in vivo and in vitro model of peritoneal fibrosis. Am. J. Physiol. Renal Physiol. 310:5 (2016), F342–F350.
32. Kahn, B.B., Alquier, T., Carling, D., Hardie, D.G., AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 1:1 (2005), 15–25.
33. Kang, H.M., Ahn, S.H., Choi, P., Ko, Y.A., Han, S.H., Chinga, F., Park, A.S., Tao, J., Sharma, K., Pullman, J., Bottinger, E.P., Goldberg, I.J., Susztak, K., Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat. Med. 21:1 (2015), 37–46.
34. Kato, M.F., Shibata, R., Obata, K., Miyachi, M., Yazawa, H., Tsuboi, K., Yamada, T., Nishizawa, T., Noda, A., Cheng, X.W., Murate, T., Koike, Y., Murohara, T., Yokota, M., Nagata, K., Pioglitazone attenuates cardiac hypertrophy in rats with salt-sensitive hypertension: role of activation of AMP-activated protein kinase and inhibition of Akt. J. Hypertens. 26:8 (2008), 1669–1676.
35. Kim, E.K., Miller, I., Aja, S., Landree, L.E., Pinn, M., McFadden, J., Kuhajda, F.P., Moran, T.H., Ronnett, G.V., C75, a fatty acid synthase inhibitor, reduces food intake via hypothalamic AMP-activated protein kinase. J. Biol. Chem. 279:19 (2004), 19970–19976.
36. Kim, H., Moon, S.Y., Kim, J.S., Baek, C.H., Kim, M., Min, J.Y., Lee, S.K., Activation of AMP-activated protein kinase inhibits ER stress and renal fibrosis. Am. J. Physiol. Renal Physiol. 308:3 (2015), F226–236.
37. King, J.D. Jr., Lee, J., Riemen, C.E., Neumann, D., Xiong, S., Foskett, J.K., Mehta, A., Muimo, R., Hallows, K.R., Role of binding and nucleoside diphosphate kinase A in the regulation of the cystic fibrosis transmembrane conductance regulator by AMP-activated protein kinase. J. Biol. Chem. 287:40 (2012), 33389–33400.
38. King, T.E. Jr., Bradford, W.Z., Castro-Bernardini, S., Fagan, E.A., Glaspole, I., Glassberg, M.K., Gorina, E., Hopkins, P.M., Kardatzke, D., Lancaster, L., Lederer, D.J., Nathan, S.D., Pereira, C.A., Sahn, S.A., Sussman, R., Swigris, J.J., Noble, P.W., Group, A.S., A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N. Engl. J. Med. 370:22 (2014), 2083–2092.
39. Konishi, M., Haraguchi, G., Ohigashi, H., Ishihara, T., Saito, K., Nakano, Y., Isobe, M., Adiponectin protects against doxorubicin-induced cardiomyopathy by anti-apoptotic effects through AMPK up-regulation. Cardiovasc. Res. 89:2 (2011), 309–319.
40. Kumar, P., Smith, T., Rahman, K., Thorn, N.E., Anania, F.A., Adiponectin agonist ADP355 attenuates CCl4-induced liver fibrosis in mice. PLoS One, 9(10), 2014, e110405.
41. Lakshmanan, A.P., Harima, M., Sukumaran, V., Soetikno, V., Thandavarayan, R.A., Suzuki, K., Kodama, M., Nagata, M., Takagi, R., Watanabe, K., Modulation of AT-1R/AMPK-MAPK cascade plays crucial role for the pathogenesis of diabetic cardiomyopathy in transgenic type 2 diabetic (Spontaneous Diabetic Torii) rats. Biochem. Pharmacol. 83:5 (2012), 653–660.
42. Lambert, G.A., Mallos, G., Zagami, A.S., Von Frey's hairs–a review of their technology and use–a novel automated von Frey device for improved testing for hyperalgesia. J. Neurosci. Methods 177:2 (2009), 420–426.
43. Lee, H.J., Feliers, D., Mariappan, M.M., Sataranatarajan, K., Choudhury, G.G., Gorin, Y., Kasinath, B.S., Tadalafil integrates nitric oxide-Hydrogen sulfide signaling to inhibit high glucose-induced matrix protein synthesis in podocytes. J. Biol. Chem. 290:19 (2015), 12014–12026.
44. Lei, H., Wu, D., Wang, J.Y., Li, L., Zhang, C.L., Feng, H., Fu, F.Y., Wu, L.L., C1q/tumor necrosis factor-related protein-6 attenuates post-infarct cardiac fibrosis by targeting RhoA/MRTF-A pathway and inhibiting myofibroblast differentiation. Basic Res. Cardiol., 110(4), 2015, 35.
45. Li, T., Jiang, S., Yang, Z., Ma, Z., Yi, W., Wang, D., Yang, Y., Targeting the energy guardian AMPK: another avenue for treating cardiomyopathy?. Cell. Mol. Life Sci., 2016.
46. Lorenz, D.R., Cantor, C.R., Collins, J.J., A network biology approach to aging in yeast. Proc. Natl. Acad. Sci. U. S. A. 106:4 (2009), 1145–1150.
47. Lu, J., Shi, J., Li, M., Gui, B., Fu, R., Yao, G., Duan, Z., Lv, Z., Yang, Y., Chen, Z., Jia, L., Tian, L., Activation of AMPK by metformin inhibits TGF-beta-induced collagen production in mouse renal fibroblasts. Life Sci. 127 (2015), 59–65.
48. Luo, T., Nocon, A., Fry, J., Sherban, A., Rui, X., Jiang, B., Xu, X.J., Han, J., Yan, Y., Yang, Q., Li, Q., Zang, M., AMPK activation by metformin suppresses abnormal extracellular matrix remodeling in adipose tissue and ameliorates insulin resistance in obesity. Diabetes 65:8 (2016), 2295–2310.
49. Ma, X., Fu, Y., Xiao, H., Song, Y., Chen, R., Shen, J., An, X., Shen, Q., Li, Z., Zhang, Y., Cardiac fibrosis alleviated by exercise training is AMPK-Dependent. PLoS One, 10(6), 2015, e0129971.
50. Malik, F.A., Meissner, A., Semenkov, I., Molinski, S., Pasyk, S., Ahmadi, S., Bui, H.H., Bear, C.E., Lidington, D., Bolz, S.S., Sphingosine-1-Phosphate is a novel regulator of cystic fibrosis transmembrane conductance regulator (CFTR) activity. PLoS One, 10(6), 2015, e0130313.
51. Mann, J.P., De Vito, R., Mosca, A., Alisi, A., Armstrong, M.J., Raponi, M., Baumann, U., Nobili, V., Portal inflammation is independently associated with fibrosis and metabolic syndrome in pediatric nonalcoholic fatty liver disease. Hepatology 63:3 (2016), 745–753.
52. Matsuo, K., Shibata, R., Ohashi, K., Kambara, T., Uemura, Y., Hiramatsu-Ito, M., Enomoto, T., Yuasa, D., Joki, Y., Ito, M., Hayakawa, S., Ogawa, H., Kihara, S., Murohara, T., Ouchi, N., Omentin functions to attenuate cardiac hypertrophic response. J. Mol. Cell. Cardiol. 79 (2015), 195–202.
53. Mia, S., Federico, G., Feger, M., Pakladok, T., Meissner, A., Voelkl, J., Groene, H.J., Alesutan, I., Lang, F., Impact of AMP-Activated protein kinase alpha1 deficiency on tissue injury following unilateral ureteral obstruction. PLoS One, 10(8), 2015, e0135235.
54. Minokoshi, Y., Kim, Y.B., Peroni, O.D., Fryer, L.G., Muller, C., Carling, D., Kahn, B.B., Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415:6869 (2002), 339–343.
55. Muanprasat, C., Sirianant, L., Sawasvirojwong, S., Homvisasevongsa, S., Suksamrarn, A., Chatsudthipong, V., Activation of AMP-activated protein kinase by a plant-derived dihydroisosteviol in human intestinal epithelial cell. Biol. Pharm. Bull. 36:4 (2013), 522–528.
56. Murca, T.M., Moraes, P.L., Capuruco, C.A., Santos, S.H., Melo, M.B., Santos, R.A., Shenoy, V., Katovich, M.J., Raizada, M.K., Ferreira, A.J., Oral administration of an angiotensin-converting enzyme 2 activator ameliorates diabetes-induced cardiac dysfunction. Regul. Pept. 177:1-3 (2012), 107–115.
57. Myerburg, M.M., King, J.D. Jr., Oyster, N.M., Fitch, A.C., Magill, A., Baty, C.J., Watkins, S.C., Kolls, J.K., Pilewski, J.M., Hallows, K.R., AMPK agonists ameliorate sodium and fluid transport and inflammation in cystic fibrosis airway epithelial cells. Am. J. Respir. Cell Mol. Biol. 42:6 (2010), 676–684.
58. Nanthakumar, C.B., Hatley, R.J., Lemma, S., Gauldie, J., Marshall, R.P., Macdonald, S.J., Dissecting fibrosis: therapeutic insights from the small-molecule toolbox. Nat. Rev. Drug Discov. 14:10 (2015), 693–720.
59. Noppe, G., Dufeys, C., Buchlin, P., Marquet, N., Castanares-Zapatero, D., Balteau, M., Hermida, N., Bouzin, C., Esfahani, H., Viollet, B., Bertrand, L., Balligand, J.L., Vanoverschelde, J.L., Beauloye, C., Horman, S., Reduced scar maturation and contractility lead to exaggerated left ventricular dilation after myocardial infarction in mice lacking AMPKalpha1. J. Mol. Cell. Cardiol. 74 (2014), 32–43.
60. Oakhill, J.S., Chen, Z.P., Scott, J.W., Steel, R., Castelli, L.A., Ling, N., Macaulay, S.L., Kemp, B.E., beta-Subunit myristoylation is the gatekeeper for initiating metabolic stress sensing by AMP-activated protein kinase (AMPK). Proc. Natl. Acad. Sci. U. S. A. 107:45 (2010), 19237–19241.
61. Park, C.S., Bang, B.R., Kwon, H.S., Moon, K.A., Kim, T.B., Lee, K.Y., Moon, H.B., Cho, Y.S., Metformin reduces airway inflammation and remodeling via activation of AMP-activated protein kinase. Biochem. Pharmacol. 84:12 (2012), 1660–1670.
62. Popper, H., History of the american association for the study of liver diseases. Hepatology 2:6 (1982), 874–878.
63. Proshkina, E.N., Shaposhnikov, M.V., Sadritdinova, A.F., Kudryavtseva, A.V., Moskalev, A.A., Basic mechanisms of longevity: a case study of Drosophila pro-longevity genes. Ageing Res. Rev. 24:Pt B (2015), 218–231.
64. Qiu, S., Xiao, Z., Piao, C., Zhang, J., Dong, Y., Cui, W., Liu, X., Zhang, Y., Du, J., AMPKalpha2 reduces renal epithelial transdifferentiation and inflammation after injury through interaction with CK2beta. J. Pathol. 237:3 (2015), 330–342.
65. Reznick, R.M., Zong, H., Li, J., Morino, K., Moore, I.K., Yu, H.J., Liu, Z.X., Dong, J., Mustard, K.J., Hawley, S.A., Befroy, D., Pypaert, M., Hardie, D.G., Young, L.H., Shulman, G.I., Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis. Cell Metab. 5:2 (2007), 151–156.
66. Salminen, A., Kaarniranta, K., AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res. Rev. 11:2 (2012), 230–241.
67. Salminen, A., Kaarniranta, K., Kauppinen, A., Age-related changes in AMPK activation: role for AMPK phosphatases and inhibitory phosphorylation by upstream signaling pathways. Ageing Res. Rev. 28 (2016), 15–26.
68. 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., Metformin attenuates lung fibrosis development via NOX4 suppression. Respir. Res., 17(1), 2016, 107.
69. Schaffer, J.M., Singh, S.K., Reitz, B.A., Zamanian, R.T., Mallidi, H.R., Single- vs double-lung transplantation in patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis since the implementation of lung allocation based on medical need. JAMA 313:9 (2015), 936–948.
70. Schmid, R., Schenker, S., Hans popper in memoriam 1903–1988. Hepatology 9:5 (1989), 669–674.
71. Smith, J.P., Cooper, T.K., McGovern, C.O., Gilius, E.L., Zhong, Q., Liao, J., Molinolo, A.A., Gutkind, J.S., Matters, G.L., Cholecystokinin receptor antagonist halts progression of pancreatic cancer precursor lesions and fibrosis in mice. Pancreas 43:7 (2014), 1050–1059.
72. Spindler, S.R., Caloric restriction: from soup to nuts. Ageing Res. Rev. 9:3 (2010), 324–353.
73. Strait, J.B., Lakatta, E.G., Aging-associated cardiovascular changes and their relationship to heart failure. Heart Fail. Clin. 8:1 (2012), 143–164.
74. Suchy, R., Pfeifer, M., [Therapeutic relevance of HRCT findings from a pneumological viewpoint]. Radiologe 54:12 (2014), 1199–1203.
75. Sun, Y., Yi, W., Yuan, Y., Lau, W.B., Yi, D., Wang, X., Wang, Y., Su, H., Wang, X., Gao, E., Koch, W.J., Ma, X.L., C1q/tumor necrosis factor-related protein-9, a novel adipocyte-derived cytokine, attenuates adverse remodeling in the ischemic mouse heart via protein kinase A activation. Circulation 128:Suppl. 1 (11) (2013), S113–120.
76. Sun, L.J., Yu, J.W., Wan, L., Zhang, X.Y., Shi, Y.G., Chen, M.Y., Endocannabinoid system activation contributes to glucose metabolism disorders of hepatocytes and promotes hepatitis C virus replication. Int. J. Infect. Dis. 23 (2014), 75–81.
77. Taguchi, Y., Ebina, M., Hashimoto, S., Ogura, T., Azuma, A., Taniguchi, H., Kondoh, Y., Suga, M., Takahashi, H., Nakata, K., Sugiyama, Y., Kudoh, S., Nukiwa, T., Pirfenidone Clinical Study Group in, J., Efficacy of pirfenidone and disease severity of idiopathic pulmonary fibrosis: extended analysis of phase III trial in Japan. Respir. Investig. 53:6 (2015), 279–287.
78. Takata, T., Motoo, Y., Tomosugi, N., Effect of Saikokeishito, a Kampo medicine, on hydrogen peroxide-induced premature senescence of normal human dermal fibroblasts. J. Integr. Med. 12:6 (2014), 495–503.
79. Tang, X., Shen, T., Jiang, X., Xia, M., Sun, X., Guo, H., Ling, W., Purified anthocyanins from bilberry and black currant attenuate hepatic mitochondrial dysfunction and steatohepatitis in mice with methionine and choline deficiency. J. Agric. Food Chem. 63:2 (2015), 552–561.
80. Wang, M., Weng, X., Guo, J., Chen, Z., Jiang, G., Liu, X., Metformin alleviated EMT and fibrosis after renal ischemia-reperfusion injury in rats. Ren. Fail. 38:4 (2016), 614–621.
81. Yang, J., Lin, S.C., Chen, G., He, L., Hu, Z., Chan, L., Trial, J., Entman, M.L., Wang, Y., Adiponectin promotes monocyte-to-fibroblast transition in renal fibrosis. J. Am. Soc. Nephrol. 24:10 (2013), 1644–1659.
82. Yang, Y., Zhao, Z., Liu, Y., Kang, X., Zhang, H., Meng, M., Suppression of oxidative stress and improvement of liver functions in mice by ursolic acid via LKB1-AMP-activated protein kinase signaling. J. Gastroenterol. Hepatol. 30:3 (2015), 609–618.
83. Yang, Y., Fan, C., Deng, C., Zhao, L., Hu, W., Di, S., Ma, Z., Zhang, Y., Qin, Z., Jin, Z., Yan, X., Jiang, S., Sun, Y., Yi, W., Melatonin reverses flow shear stress-induced injury in bone marrow mesenchymal stem cells via activation of AMP-activated protein kinase signaling. J. Pineal Res. 60:2 (2016), 228–241.
84. Yi, W., Sun, Y., Yuan, Y., Lau, W.B., Zheng, Q., Wang, X., Wang, Y., Shang, X., Gao, E., Koch, W.J., Ma, X.L., C1q/tumor necrosis factor-related protein-3, a newly identified adipokine, is a novel antiapoptotic, proangiogenic, and cardioprotective molecule in the ischemic mouse heart. Circulation 125:25 (2012), 3159–3169.
85. Yuan, F., Liu, Y.H., Liu, F.Y., Peng, Y.M., Tian, J.W., Intraperitoneal administration of the globular adiponectin gene ameliorates diabetic nephropathy in Wistar rats. Mol. Med. Rep. 9:6 (2014), 2293–2300.
86. Yuan, Y., Lau, W.B., Su, H., Sun, Y., Yi, W., Du, Y., Christopher, T., Lopez, B., Wang, Y., Ma, X.L., C1q-TNF-related protein-9, a novel cardioprotetcive cardiokine, requires proteolytic cleavage to generate a biologically active globular domain isoform. Am. J. Physiol. Endocrinol. Metab. 308:10 (2015), E891–898.
87. Zhang, P., Hu, X., Xu, X., Fassett, J., Zhu, G., Viollet, B., Xu, W., Wiczer, B., Bernlohr, D.A., Bache, R.J., Chen, Y., AMP activated protein kinase-alpha2 deficiency exacerbates pressure-overload-induced left ventricular hypertrophy and dysfunction in mice. Hypertension 52:5 (2008), 918–924.
88. Zhang, C.X., Pan, S.N., Meng, R.S., Peng, C.Q., Xiong, Z.J., Chen, B.L., Chen, G.Q., Yao, F.J., Chen, Y.L., Ma, Y.D., Dong, Y.G., Metformin attenuates ventricular hypertrophy by activating the AMP-activated protein kinase-endothelial nitric oxide synthase pathway in rats. Clin. Exp. Pharmacol. Physiol. 38:1 (2011), 55–62.
89. Zhang, W., Wu, R., Zhang, F., Xu, Y., Liu, B., Yang, Y., Zhou, H., Wang, L., Wan, K., Xiao, X., Zhang, X., Thiazolidinediones improve hepatic fibrosis in rats with non-alcoholic steatohepatitis by activating the adenosine monophosphate-activated protein kinase signalling pathway. Clin. Exp. Pharmacol. Physiol. 39:12 (2012), 1026–1033.
90. Zhang, Y., Mi, S.L., Hu, N., Doser, T.A., Sun, A., Ge, J., Ren, J., Mitochondrial aldehyde dehydrogenase 2 accentuates aging-induced cardiac remodeling and contractile dysfunction: role of AMPK, Sirt1, and mitochondrial function. Free Radic. Biol. Med. 71 (2014), 208–220.
91. Zhang, Z., Wang, F., Wang, B.J., Chu, G., Cao, Q., Sun, B.G., Dai, Q.Y., Inhibition of leptin-induced vascular extracellular matrix remodelling by adiponectin. J. Mol. Endocrinol. 53:2 (2014), 145–154.
92. Zhang, Y., Vasheghani, F., Li, Y.H., Blati, M., Simeone, K., Fahmi, H., Lussier, B., Roughley, P., Lagares, D., Pelletier, J.P., Martel-Pelletier, J., Kapoor, M., Cartilage-specific deletion of mTOR upregulates autophagy and protects mice from osteoarthritis. Ann. Rheum. Dis. 74:7 (2015), 1432–1440.
93. Zheng, Q., Yuan, Y., Yi, W., Lau, W.B., Wang, Y., Wang, X., Sun, Y., Lopez, B.L., Christopher, T.A., Peterson, J.M., Wong, G.W., Yu, S., Yi, D., Ma, X.L., C1q/TNF-related proteins, a family of novel adipokines, induce vascular relaxation through the adiponectin receptor-1/AMPK/eNOS/nitric oxide signaling pathway. Arterioscler. Thromb. Vasc. Biol. 31:11 (2011), 2616–2623.
94. da Silva Morais, A., Abarca-Quinones, J., Guigas, B., Viollet, B., Starkel, P., Horsmans, Y., Leclercq, I.A., Development of hepatic fibrosis occurs normally in AMPK-deficient mice. Clin. Sci. (Lond.) 118:6 (2010), 411–420.