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Publication : Regulation of hepatic stellate cell differentiation by the neurotrophin receptor p75NTR.

First Author  Passino MA Year  2007
Journal  Science Volume  315
Issue  5820 Pages  1853-6
PubMed ID  17395831 Mgi Jnum  J:120368
Mgi Id  MGI:3706450 Doi  10.1126/science.1137603
Citation  Passino MA, et al. (2007) Regulation of hepatic stellate cell differentiation by the neurotrophin receptor p75NTR. Science 315(5820):1853-6
abstractText  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 p75NTR, 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 p75NTR exacerbated liver pathology and inhibited hepatocyte proliferation in vivo. p75NTR-/- HSCs failed to differentiate to myofibroblasts and did not support hepatocyte proliferation. Moreover, inhibition of p75NTR signaling to the small guanosine triphosphatase Rho resulted in impaired HSC differentiation. Our results identify signaling from p75NTR to Rho as a mechanism for the regulation of HSC differentiation to regeneration-promoting cells that support hepatocyte proliferation in the diseased liver.
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