Regulation of Hepatic Stellate Cell Differentiation by the Neurotrophin Receptor$\text{p}75^{\text{NTR}}

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$\text{p}75^{\text{NTR}}$, a tumor necrosis factor receptor superfamily membe...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2007-03, Vol.315 (5820), p.1853-1856
Main Authors: Passino, Melissa A., Adams, Ryan A., Sikorski, Shoana L., Akassoglou, Katerina
Format: Article
Language:English
Subjects:
Apoptosis
Fibrosis
Hepatocytes
Liver
Liver cells
Liver diseases
Myofibroblasts
Neurons
Physiological regulation
Receptors
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Summary: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$\text{p}75^{\text{NTR}}$, 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$\text{p}75^{\text{NTR}}$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$\text{p}75^{\text{NTR}}$signaling to the small guanosine triphosphatase Rho resulted in impaired HSC differentiation. Our results identify signaling from$\text{p}75^{\text{NTR}}$to Rho as a mechanism for the regulation of HSC differentiation to regeneration-promoting cells that support hepatocyte proliferation in the diseased liver.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1137603