Lookup NU author(s): Professor Fiona Oakley,
Professor Jelena Mann,
Professor Derek Mann
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
JunD is implicated in the regulation of hepatic stellate cell (HSC) activation and liver fibrosis via its transcriptional regulation of the tissue inhibitor of metalloproteinases-1 (TIMP-1) gene. In the present study we found in vivo evidence of a role for JunD in fibrogenesis. Expression of JunD was demonstrated in alpha-SMA-positive activated HSCs of fibrotic rodents and human livers. The junD-/- mice were protected from carbon tetrachloride-induced fibrosis. The livers of injured junD-/- mice displayed significantly reduced formation of fibrotic crosslinked collagen and a smaller number of alpha-SMA-positive HSCs compared with those of wild-type (wt) mice. Hepatic TIMP-1 mRNA expression in injured junD-/- mice was 78% lower and in culture activated junD-/- HSCs was 50%-80% lower than that in wt mice. In examining the signal transduction mechanisms that regulate JunD-dependent TIMP-1 expression, we found a role for phosphorylation of the Ser100 residue of JunD but ruled out JNK as a mediator of this event, suggesting ERK1/2 is utilized. In conclusion, a signaling pathway for the development of fibrosis involves the regulation of TIMP-1 expression by phosphorylated JunD. Copyright © 2006 by the American Association for the Study of Liver Diseases.
Author(s): Smart DE, Green K, Oakley F, Weitzman JB, Yaniv M, Reynolds G, Mann J, Millward-Sadler H, Mann DA
Publication type: Article
Publication status: Published
ISSN (print): 0270-9139
ISSN (electronic): 1527-3350
Publisher: John Wiley & Sons, Inc.
PubMed id: 17133482
Altmetrics provided by Altmetric