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Licensed Unlicensed Requires Authentication Published by De Gruyter January 12, 2016

Activation of corticotropin releasing factor receptors up regulates collagen production by hepatic stellate cells via promoting p300 expression

  • Changzhen Wang , Shan Yang EMAIL logo , Jingjing Huang , Songlin Chen , Yuan Li and Quanqiang Li
From the journal Biological Chemistry


Liver fibrosis is characterized with the over expression and excessive accumulation of extracellular matrix proteins, including collagens. The causative factors in the over production of collagens are not fully understood. This study aims to test a hypothesis that activation of corticotropin releasing factor receptors up regulates the expression of collagen in hepatic stellate cells. In this study, human hepatic stellate cell line, LX-2 cells were cultured. Expression of collagens by LX-2 cells was assessed by real time RT-PCR, Western blotting. The results showed that, upon exposure to urocortin in the culture, LX-2 cells (a human hepatic stellate cell line) increased the expression of collagen IV (Col4) markedly. The exposure to urocortin also enhanced the levels of pTip60, H3K9, RNA polymerase II and forkhead box protein 3 at the collagen promoter locus as well as increase in the expression of Col4 mRNA and protein in the cells. Blocking p300 efficiently suppressed the urocortin-induced Col4 expression in LX-2 cells and unveiled an apoptosis-inducing effect of urocortin. In conclusion, activation of CRF receptors is capable of enforcing the production of Col4 by LX-2 cells via up regulating the p300 pathway, which may contribute to the development of liver fibrosis.

Award Identifier / Grant number: #81360598

Funding statement: This work was supported by a grant from the National Natural Science Foundation of China (#81360598).


This work was supported by a grant from the National Natural Science Foundation of China (#81360598).

  1. Conflict of interest statement: None to declare.


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Received: 2015-8-23
Accepted: 2015-12-30
Published Online: 2016-1-12
Published in Print: 2016-5-1

©2016 by De Gruyter

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