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Anti-fibrogenic strategies and the regression of fibrosis

Best Pract Res Clin Gastroenterol. 2011 Apr;25(2):305-17. doi: 10.1016/j.bpg.2011.02.011.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Cell Transplantation*
  • Epithelial-Mesenchymal Transition
  • Extracellular Matrix / metabolism
  • Hepatic Stellate Cells / pathology
  • Humans
  • Liver / cytology*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / therapy*
  • Myofibroblasts / cytology
  • Myofibroblasts / pathology*
  • Renin-Angiotensin System
  • Toll-Like Receptor 4 / antagonists & inhibitors

Substances

  • Toll-Like Receptor 4