p38 MAPK mediates the regulation of α1(I) procollagen mRNA levels by TNF-α and TGF-β in a cell line of rat hepatic stellate cells
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Wiley / Federation of European Biochemical Societies
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Abstract
The role of members of the mitogen-activated protein kinase (MAPK) family on tumor necrosis factor alpha (TNF-alpha)-mediated down-regulation of col1a1 gene was studied. TNF-alpha increased extracellular-regulated kinase and Jun-N-terminal kinase phosphorylation, but these effects were not related to its inhibitory effect on alpha1(I) procollagen (col1a1) mRNA levels. Phosphorylation of p38 MAPK was decreased in response to TNF-alpha, and the specific p38 MAPK inhibitor SB203580 mimicked the effect of TNF-alpha on col1a1 mRNA levels. Transforming growth factor beta (TGF-beta) increased p38 MAPK phosphorylation and SB203580 prevented the induction of col1a1 mRNA levels by TGF-beta. These results suggest that p38 MAPK plays an important role in regulating the expression of col1a1 in hepatic stellate cells in response to cytokines.
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In this report our results indicate that p38 MAPK is a keymediator of the anti-fibrogenic efect of TNF-alpha and the profibrogenic efect of TBF-beta in HSC.
This is the peer reviewed version of the following article: Varela-Rey, Montiel-Duarte, Osés-Prieto, López-Zabalza, Jaffrèzou, Rojkind, & Iraburu. (2002). p38 MAPK mediates the regulation of α1(I) procollagen mRNA levels by TNF-α and TGF-β in a cell line of rat hepatic stellate cells. FEBS Letters, 528(1-3), 133-138, which has been published in final form at https://doi.org/10.1016/S0014-5793(02)03276-3. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
Bibliographic citation
Varela-Rey, Montiel-Duarte, Osés-Prieto, López-Zabalza, Jaffrèzou, Rojkind, & Iraburu. (2002). p38 MAPK mediates the regulation of α1(I) procollagen mRNA levels by TNF-α and TGF-β in a cell line of rat hepatic stellate cells. FEBS Letters, 528(1-3), 133-138. https://doi.org/10.1016/S0014-5793(02)03276-3
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Fondo de Investigaciones Sanitarias (FIS) Grant 00/0143 and NIH Grant AA 10541
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Attribution-NonCommercial-NoDerivatives 4.0 International