Osteopontin is induced by hedgehog pathway activation and promotes fibrosis progression in nonalcoholic steatohepatitis

Wing-Kin Syn, Steve S Choi, Evaggelia Liaskou, Gamze F Karaca, Kolade M Agboola, Ye Htun Oo, Zhiyong Mi, Thiago A Pereira, Marzena Zdanowicz, Padmini Malladi, Yuping Chen, Cynthia Moylan, Youngmi Jung, Syamal D Bhattacharya, Vanessa Teaberry, Alessia Omenetti, Manal F Abdelmalek, Cynthia D Guy, David H Adams, Paul C KuoGregory A Michelotti, Peter F Whitington, Anna Mae Diehl

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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 languageEnglish
Pages (from-to)106-15
Number of pages10
Issue number1
Early online date21 Oct 2010
Publication statusPublished - Jan 2011

Bibliographical note

Copyright © 2010 American Association for the Study of Liver Diseases.


  • 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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