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Semin Liver Dis 2010; 30(3): 226-231
DOI: 10.1055/s-0030-1255352
© Thieme Medical Publishers

Cell Death and Fibrogenesis

Wajahat Mehal1 , Avlin Imaeda1
  • 1Section of Digestive Diseases, Yale University, New Haven, Connecticut
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Publication History

Publication Date:
21 July 2010 (online)

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ABSTRACT

Fibrosis is a common feature of chronic liver injury and is initiated by cell death inside the liver. Hepatocyte death results in apoptotic bodies and other cellular debris, which are phagocytosed by hepatic stellate cells (HSCs), resulting in their activation, proliferation, differentiation, and matrix deposition. This profibrotic effect of cellular death is balanced by an antifibrotic effect of HSC death. Many HSC survival signals are obtained from the extracellular matrix, and active proapoptotic signals are provided by immune cells, particularly natural killer (NK) cells. Quiescent HSCs are relatively resistant to apoptotic signals but become sensitive after activation. The important role of NK cells in inducing HSC apoptosis may explain the increased fibrosis associated with immune suppression (e.g., in the transplant recipient) and HIV infection. HSCs also undergo senescence, which limits their function and sensitizes them to apoptosis.

KEYWORDS

Hepatic stellate cells - fibrosis - cell death - apoptosis

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Wajahat MehalM.D. D.Phil. 

Section of Digestive Diseases, Yale University

333 Cedar Street/1080 LMP, P.O. Box 208019, New Haven, CT 06520-8019

Email: Wajahat.mehal@yale.edu

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