Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Science 315 (5820): 1853-1856

Copyright © 2007 by the American Association for the Advancement of Science

Regulation of Hepatic Stellate Cell Differentiation by the Neurotrophin Receptor p75NTR

Melissa A. Passino, Ryan A. Adams, Shoana L. Sikorski, Katerina Akassoglou*

Abstract: 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.

Department of Pharmacology, University of California, San Diego (UCSD), La Jolla, CA 92093–0636, USA.

* To whom correspondence should be addressed. E-mail: akass{at}ucsd.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
p75 neurotrophin receptor regulates glucose homeostasis and insulin sensitivity.
B. Baeza-Raja, P. Li, N. Le Moan, B. D. Sachs, C. Schachtrup, D. Davalos, E. Vagena, D. Bridges, C. Kim, A. R. Saltiel, et al. (2012)
PNAS 109, 5838-5843
   Abstract »    Full Text »    PDF »
Hepatic Stellate Cell-derived Delta-like Homolog 1 (DLK1) Protein in Liver Regeneration.
N.-L. Zhu, K. Asahina, J. Wang, A. Ueno, R. Lazaro, Y. Miyaoka, A. Miyajima, and H. Tsukamoto (2012)
J. Biol. Chem. 287, 10355-10367
   Abstract »    Full Text »    PDF »
Depletion of activated hepatic stellate cell correlates with severe liver damage and abnormal liver regeneration in acetaminophen-induced liver injury.
K. Shen, W. Chang, X. Gao, H. Wang, W. Niu, L. Song, and X. Qin (2011)
Acta Biochim Biophys Sin 43, 307-315
   Abstract »    Full Text »    PDF »
Fibrinogen Triggers Astrocyte Scar Formation by Promoting the Availability of Active TGF-{beta} after Vascular Damage.
C. Schachtrup, J. K. Ryu, M. J. Helmrick, E. Vagena, D. K. Galanakis, J. L. Degen, R. U. Margolis, and K. Akassoglou (2010)
J. Neurosci. 30, 5843-5854
   Abstract »    Full Text »    PDF »
Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex.
K. Namekata, C. Harada, C. Taya, X. Guo, H. Kimura, L. F. Parada, and T. Harada (2010)
PNAS 107, 7586-7591
   Abstract »    Full Text »    PDF »
Hepatocyte nuclear factor 4{alpha} attenuates hepatic fibrosis in rats.
H.-Y. Yue, C. Yin, J.-L. Hou, X. Zeng, Y.-X. Chen, W. Zhong, P.-F. Hu, X. Deng, Y.-X. Tan, J.-P. Zhang, et al. (2010)
Gut 59, 236-246
   Abstract »    Full Text »    PDF »
Plasmin-mediated Proteolysis Is Required for Hepatocyte Growth Factor Activation during Liver Repair.
K. Shanmukhappa, U. Matte, J. L. Degen, and J. A. Bezerra (2009)
J. Biol. Chem. 284, 12917-12923
   Abstract »    Full Text »    PDF »
p75 neurotrophin receptor regulates agonist-induced pulmonary vasoconstriction.
M. Xu, C. V. Remillard, B. D. Sachs, A. Makino, O. Platoshyn, W. Yao, W. H. Dillmann, K. Akassoglou, and J. X.-J. Yuan (2008)
Am J Physiol Heart Circ Physiol 295, H1529-H1538
   Abstract »    Full Text »    PDF »
Functional Role of Sortilin in Myogenesis and Development of Insulin-responsive Glucose Transport System in C2C12 Myocytes.
M. Ariga, T. Nedachi, H. Katagiri, and M. Kanzaki (2008)
J. Biol. Chem. 283, 10208-10220
   Abstract »    Full Text »    PDF »
Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver.
S. L. Friedman (2008)
Physiol Rev 88, 125-172
   Abstract »    Full Text »    PDF »
p75 neurotrophin receptor regulates tissue fibrosis through inhibition of plasminogen activation via a PDE4/cAMP/PKA pathway.
B. D. Sachs, G. S. Baillie, J. R. McCall, M. A. Passino, C. Schachtrup, D. A. Wallace, A. J. Dunlop, K. F. MacKenzie, E. Klussmann, M. J. Lynch, et al. (2007)
J. Cell Biol. 177, 1119-1132
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882