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IL-13 induces connective tissue growth factor in rat hepatic stellate cells via TGF-beta-independent Smad signaling.

Authors: Liu, Y  Meyer, C  Muller, A  Herweck, F  Li, Q  Mullenbach, R  Mertens, PR  Dooley, S  Weng, HL 
Citation: Liu Y, etal., J Immunol. 2011 Sep 1;187(5):2814-23. Epub 2011 Jul 29.
Pubmed: (View Article at PubMed) PMID:21804025
DOI: Full-text: DOI:10.4049/jimmunol.1003260

Connective tissue growth factor (CTGF) plays a central role in stimulating extracellular matrix deposition in the liver, and hence is considered a critical mediator of TGF-beta-dependent fibrogenesis. Hepatic stellate cells (HSCs) are known as the major source of CTGF in damaged liver. However, previous studies revealed that IL-13, rather than TGF-beta, represents the predominant inducer of CTGF expression in HSCs. We now dissected IL-13 downstream signaling that modulates CTGF expression in HSCs. IL-13 induces a time- and dosage-dependent increase of CTGF in a TGF-beta-independent manner. This process requires participation of different Smad proteins and their upstream receptor kinases (activin receptor-like kinases). Smad1 and Smad2 were identified as the key mediators of IL-13-dependent CTGF expression. Furthermore, IL-13 induces Stat6 phosphorylation in HSCs, but Stat6 was not involved in CTGF induction. Instead, the Erk1/2-MAPK pathway was found to be responsible for IL-13-induced early Smad phosphorylation and CTGF synthesis. We demonstrate that IL-13 induces CTGF expression in HSCs by activating TGF-beta-independent activin receptor-like kinase/Smad signaling via the Erk-MAPK pathway rather than via its canonical JAK/Stat6 pathway. These results provide an improved new insight into the molecular mechanisms of profibrotic IL-13 activities in the liver.

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RGD Object Information
RGD ID: 5684373
Created: 2011-12-16
Species: All species
Last Modified: 2011-12-16
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.