Anti-fibrogenic Strategies and the Regression of Fibrosis

Overview

Journal Best Pract Res Clin Gastroenterol

Publisher Elsevier

Specialty Gastroenterology

Date 2011 Apr 19

PMID 21497747

Citations 84

Authors

Tatiana Kisseleva

David A Brenner

Affiliations

Soon will be listed here.

Abstract

Liver fibrosis is an outcome of many chronic diseases, and often results in cirrhosis, liver failure, and portal hypertension. Liver transplantation is the only treatment available for patients with advanced stage of fibrosis. Therefore, alternative methods are required to develop new strategies for anti-fibrotic therapy. Available treatments are designed to substitute for liver transplantation or bridge the patients, they include inhibitors of fibrogenic cytokines such as TGF-β1 and EGF, inhibitors of rennin angiotensin system, and blockers of TLR4 signalling. Development of liver fibrosis is orchestrated by many cell types. However, activated myofibroblasts remain the primary target for anti-fibrotic therapy. Hepatic stellate cells and portal fibroblasts are considered to play a major role in development of liver fibrosis. Here we discuss the origin of activated myofibroblasts and different aspects of their activation, differentiation and potential inactivation during regression of liver fibrosis.

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References

Choi S, Diehl A . Epithelial-to-mesenchymal transitions in the liver. Hepatology. 2009; 50(6):2007-13. PMC: 2787916. DOI: 10.1002/hep.23196. View

Omenetti A, Porrello A, Jung Y, Yang L, Popov Y, Choi S . Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans. J Clin Invest. 2008; 118(10):3331-42. PMC: 2542850. DOI: 10.1172/JCI35875. View

Czaja A, Carpenter H . Decreased fibrosis during corticosteroid therapy of autoimmune hepatitis. J Hepatol. 2004; 40(4):646-52. DOI: 10.1016/j.jhep.2004.01.009. View

Alison M, Islam S, Lim S . Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly. J Pathol. 2008; 217(2):282-98. DOI: 10.1002/path.2453. View

Yovchev M, Zhang J, Neufeld D, Grozdanov P, Dabeva M . Thymus cell antigen-1-expressing cells in the oval cell compartment. Hepatology. 2009; 50(2):601-11. DOI: 10.1002/hep.23012. View

Simmons P, Przepiorka D, Thomas E, Torok-Storb B . Host origin of marrow stromal cells following allogeneic bone marrow transplantation. Nature. 1987; 328(6129):429-32. DOI: 10.1038/328429a0. View

Trobridge P, Knoblaugh S, Washington M, Munoz N, Tsuchiya K, Rojas A . TGF-beta receptor inactivation and mutant Kras induce intestinal neoplasms in mice via a beta-catenin-independent pathway. Gastroenterology. 2009; 136(5):1680-8.e7. PMC: 2782436. DOI: 10.1053/j.gastro.2009.01.066. View

Tsukamoto H . Adipogenic phenotype of hepatic stellate cells. Alcohol Clin Exp Res. 2005; 29(11 Suppl):132S-133S. DOI: 10.1097/01.alc.0000189279.92602.f0. View

Schurch W, Seemayer T, Gabbiani G . The myofibroblast: a quarter century after its discovery. Am J Surg Pathol. 1998; 22(2):141-7. DOI: 10.1097/00000478-199802000-00001. View

10.

van Poll D, Parekkadan B, Cho C, Berthiaume F, Nahmias Y, Tilles A . Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo. Hepatology. 2008; 47(5):1634-43. DOI: 10.1002/hep.22236. View

11.

Asahina K, Tsai S, Li P, Ishii M, Maxson Jr R, Sucov H . Mesenchymal origin of hepatic stellate cells, submesothelial cells, and perivascular mesenchymal cells during mouse liver development. Hepatology. 2008; 49(3):998-1011. PMC: 2673117. DOI: 10.1002/hep.22721. View

12.

Subeq Y, Ke C, Lin N, Lee C, Chiu Y, Hsu B . Valsartan decreases TGF-β1 production and protects against chlorhexidine digluconate-induced liver peritoneal fibrosis in rats. Cytokine. 2010; 53(2):223-30. DOI: 10.1016/j.cyto.2010.11.004. View

13.

Ramachandran P, Iredale J . Reversibility of liver fibrosis. Ann Hepatol. 2009; 8(4):283-91. View

14.

Sato Y, Murase K, Kato J, Kobune M, Sato T, Kawano Y . Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone. Nat Biotechnol. 2008; 26(4):431-42. DOI: 10.1038/nbt1396. View

15.

Soto-Gutierrez A, Navarro-Alvarez N, Yagi H, Yarmush M . Stem cells for liver repopulation. Curr Opin Organ Transplant. 2009; 14(6):667-73. PMC: 3725723. DOI: 10.1097/MOT.0b013e3283328070. View

16.

Kweon Y, Goodman Z, Dienstag J, Schiff E, Brown N, Burchardt E . Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B. J Hepatol. 2001; 35(6):749-55. DOI: 10.1016/s0168-8278(01)00218-5. View

17.

Kallis Y, Forbes S . The bone marrow and liver fibrosis: friend or foe?. Gastroenterology. 2009; 137(4):1218-21. DOI: 10.1053/j.gastro.2009.08.026. View

18.

Zeisberg E, Potenta S, Sugimoto H, Zeisberg M, Kalluri R . Fibroblasts in kidney fibrosis emerge via endothelial-to-mesenchymal transition. J Am Soc Nephrol. 2008; 19(12):2282-7. PMC: 2588112. DOI: 10.1681/ASN.2008050513. View

19.

Hashimoto N, Jin H, Liu T, Chensue S, Phan S . Bone marrow-derived progenitor cells in pulmonary fibrosis. J Clin Invest. 2004; 113(2):243-52. PMC: 310750. DOI: 10.1172/JCI18847. View

20.

Terry C, Mitry R, Lehec S, Muiesan P, Rela M, Heaton N . The effects of cryopreservation on human hepatocytes obtained from different sources of liver tissue. Cell Transplant. 2005; 14(8):585-94. DOI: 10.3727/000000005783982765. View