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Abstract
Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. Recently, we showed that NASH-related cirrhosis is associated with Hedgehog (Hh) pathway activation. The gene encoding osteopontin (OPN), a profibrogenic extracellular matrix protein and cytokine, is a direct transcriptional target of the Hh pathway. Thus, we hypothesize that Hh signaling induces OPN to promote liver fibrosis in NASH. Hepatic OPN expression and liver fibrosis were analyzed in wild-type (WT) mice, Patched-deficient (Ptc(+/-) ) (overly active Hh signaling) mice, and OPN-deficient mice before and after feeding methionine and choline-deficient (MCD) diets to induce NASH-related fibrosis. Hepatic OPN was also quantified in human NASH and nondiseased livers. Hh signaling was manipulated in cultured liver cells to assess direct effects on OPN expression, and hepatic stellate cells (HSCs) were cultured in medium with different OPN activities to determine effects on HSC phenotype. When fed MCD diets, Ptc(+/-) mice expressed more OPN and developed worse liver fibrosis (P
Original language | English |
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Pages (from-to) | 106-15 |
Number of pages | 10 |
Journal | Hepatology |
Volume | 53 |
Issue number | 1 |
Early online date | 21 Oct 2010 |
DOIs | |
Publication status | Published - Jan 2011 |
Bibliographical note
Copyright © 2010 American Association for the Study of Liver Diseases.Keywords
- Animals
- Cell Line
- Choline Deficiency
- Diet
- Fatty Liver
- Hedgehog Proteins
- Hepatic Stellate Cells
- Humans
- Liver Cirrhosis
- Methionine
- Mice
- Mice, Inbred C57BL
- Osteopontin
- Up-Regulation
- Veratrum Alkaloids
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Dive into the research topics of 'Osteopontin is induced by hedgehog pathway activation and promotes fibrosis progression in nonalcoholic steatohepatitis'. Together they form a unique fingerprint.Projects
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The Molecular Basis of Regulatory T Cell Recruitment to the Inflamed Liver
Adams, D. (Principal Investigator)
2/10/06 → 30/09/09
Project: Research Councils