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The simple truth is seldom true and never simple: Dual role for p75 NTR in transdifferentation and cell death of hepatic stellate cells
Author(s) -
Geerts Albert
Publication year - 2007
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21861
Subject(s) - hepatic stellate cell , microbiology and biotechnology , hepatocyte , liver regeneration , biology , hepatocyte growth factor , regeneration (biology) , liver injury , cellular differentiation , cell growth , cancer research , receptor , endocrinology , in vitro , biochemistry , genetics , gene
Differentiation of hepatic stellate cells (HSCs) to extracellular matrix- and growth factor-producing cells supports liver regeneration through promotion of hepatocyte proliferation. We show that the neurotrophin receptor p75(NTR), a tumor necrosis factor receptor superfamily member expressed in HSCs after fibrotic and cirrhotic liver injury in humans, is a regulator of liver repair. In mice, depletion of p75(NTR) exacerbated liver pathology and inhibited hepatocyte proliferation in vivo. p75 (NTR-/-) HSCs failed to differentiate to myofibroblasts and did not support hepatocyte proliferation. Moreover, inhibition of p75(NTR) signaling to the small guanosine triphosphatase Rho resulted in impaired HSC differentiation. Our results identify signaling from p75(NTR) to Rho as a mechanism for the regulation of HSC differentiation to regeneration-promoting cells that support hepatocyte proliferation in the diseased liver.