Autophagy: A New Therapeutic Target for Liver Fibrosis

Overview

Journal World J Hepatol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2015 Aug 12

PMID 26261688

Citations 20

Authors

Yu-Qing Mao

Xiao-Ming Fan

Affiliations

Soon will be listed here.

Abstract

Hepatic fibrosis is a wound-healing response to liver injury and the result of imbalance of extracellular matrix (ECM) accumulation and degradation. The relentless production and progressive accumulation of ECM can lead to end-stage liver disease. Although significant progress has been achieved in elucidating the mechanisms of fibrogenesis, effective anti-fibrotic strategies are still lacking. Autophagy is an intracellular process of self-digestion of defective organelles to provide material recycling or energy for cell survival. Autophagy has been implicated in the pathophysiology of many human disorders including hepatic fibrosis. However, the exact relationships between autophagy and hepatic fibrosis are not totally clear and need further investigations. A new therapeutic target for liver fibrosis could be developed with a better understanding of autophagy.

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References

Gabele E, Reif S, Tsukada S, Bataller R, Yata Y, Morris T . The role of p70S6K in hepatic stellate cell collagen gene expression and cell proliferation. J Biol Chem. 2005; 280(14):13374-82. DOI: 10.1074/jbc.M409444200. View

Ishida Y, Yamamoto A, Kitamura A, Lamande S, Yoshimori T, Bateman J . Autophagic elimination of misfolded procollagen aggregates in the endoplasmic reticulum as a means of cell protection. Mol Biol Cell. 2009; 20(11):2744-54. PMC: 2688553. DOI: 10.1091/mbc.e08-11-1092. View

Hou W, Han J, Lu C, Goldstein L, Rabinowich H . Autophagic degradation of active caspase-8: a crosstalk mechanism between autophagy and apoptosis. Autophagy. 2010; 6(7):891-900. PMC: 3039736. DOI: 10.4161/auto.6.7.13038. View

Hsu C, Schwabe R . Autophagy and hepatic stellate cell activation - partners in crime?. J Hepatol. 2011; 55(6):1176-7. DOI: 10.1016/j.jhep.2011.08.001. View

Choi M, Ding Y, Kim S . TGF-β signaling via TAK1 pathway: role in kidney fibrosis. Semin Nephrol. 2012; 32(3):244-52. PMC: 3407377. DOI: 10.1016/j.semnephrol.2012.04.003. View

Ding W, Li M, Chen X, Ni H, Lin C, Gao W . Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis in mice. Gastroenterology. 2010; 139(5):1740-52. PMC: 4129642. DOI: 10.1053/j.gastro.2010.07.041. View

Iredale J, Thompson A, Henderson N . Extracellular matrix degradation in liver fibrosis: Biochemistry and regulation. Biochim Biophys Acta. 2012; 1832(7):876-83. DOI: 10.1016/j.bbadis.2012.11.002. View

Thoen L, Guimaraes E, Dolle L, Mannaerts I, Najimi M, Sokal E . A role for autophagy during hepatic stellate cell activation. J Hepatol. 2011; 55(6):1353-60. DOI: 10.1016/j.jhep.2011.07.010. View

Patsenker E, Schneider V, Ledermann M, Saegesser H, Dorn C, Hellerbrand C . Potent antifibrotic activity of mTOR inhibitors sirolimus and everolimus but not of cyclosporine A and tacrolimus in experimental liver fibrosis. J Hepatol. 2010; 55(2):388-98. DOI: 10.1016/j.jhep.2010.10.044. View

10.

Gummert J, Ikonen T, Morris R . Newer immunosuppressive drugs: a review. J Am Soc Nephrol. 1999; 10(6):1366-80. DOI: 10.1681/ASN.V1061366. View

11.

Kiyono K, Suzuki H, Matsuyama H, Morishita Y, Komuro A, Kano M . Autophagy is activated by TGF-beta and potentiates TGF-beta-mediated growth inhibition in human hepatocellular carcinoma cells. Cancer Res. 2009; 69(23):8844-52. DOI: 10.1158/0008-5472.CAN-08-4401. View

12.

Aranguiz-Urroz P, Canales J, Copaja M, Troncoso R, Vicencio J, Carrillo C . Beta(2)-adrenergic receptor regulates cardiac fibroblast autophagy and collagen degradation. Biochim Biophys Acta. 2010; 1812(1):23-31. DOI: 10.1016/j.bbadis.2010.07.003. View

13.

Schluger L, Sheiner P, Thung S, Lau J, Min A, Wolf D . Severe recurrent cholestatic hepatitis C following orthotopic liver transplantation. Hepatology. 1996; 23(5):971-6. DOI: 10.1002/hep.510230505. View

14.

Wu D, Cederbaum A . Inhibition of autophagy promotes CYP2E1-dependent toxicity in HepG2 cells via elevated oxidative stress, mitochondria dysfunction and activation of p38 and JNK MAPK. Redox Biol. 2013; 1:552-65. PMC: 3836279. DOI: 10.1016/j.redox.2013.10.008. View

15.

Friedman S . Mechanisms of hepatic fibrogenesis. Gastroenterology. 2008; 134(6):1655-69. PMC: 2888539. DOI: 10.1053/j.gastro.2008.03.003. View

16.

Das F, Bera A, Ghosh-Choudhury N, Abboud H, Kasinath B, Ghosh Choudhury G . TGFβ-induced deptor suppression recruits mTORC1 and not mTORC2 to enhance collagen I (α2) gene expression. PLoS One. 2014; 9(10):e109608. PMC: 4198127. DOI: 10.1371/journal.pone.0109608. View

17.

Neef M, Ledermann M, Saegesser H, Schneider V, Reichen J . Low-dose oral rapamycin treatment reduces fibrogenesis, improves liver function, and prolongs survival in rats with established liver cirrhosis. J Hepatol. 2006; 45(6):786-96. DOI: 10.1016/j.jhep.2006.07.030. View

18.

Zhang Y, Qi H, Taylor R, Xu W, Liu L, Jin S . The role of autophagy in mitochondria maintenance: characterization of mitochondrial functions in autophagy-deficient S. cerevisiae strains. Autophagy. 2007; 3(4):337-46. DOI: 10.4161/auto.4127. View

19.

Wang Y, Singh R, Xiang Y, Czaja M . Macroautophagy and chaperone-mediated autophagy are required for hepatocyte resistance to oxidant stress. Hepatology. 2010; 52(1):266-77. PMC: 2924621. DOI: 10.1002/hep.23645. View

20.

Yin X, Ding W, Gao W . Autophagy in the liver. Hepatology. 2008; 47(5):1773-85. DOI: 10.1002/hep.22146. View