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

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 t...

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Bibliographic Details
Authors: Varela Rey, Marta María, Montiel-Duarte, Cristina, Osés-Prieto, Juan Antonio, López-Zabalza, María Jesús, Jaffrèzou, J. P., Rojkind, Marcos, Iraburu, María José
Format: article
Publication Date:2002
Country:España
Institution:Universidad de Santiago de Compostela (USC)
Repository:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Language:English
OAI Identifier:oai:minerva.usc.gal:10347/39359
Online Access:https://hdl.handle.net/10347/39359
Access Level:Open access
Keyword:p38 MAPK
TNF-alpha
TGF-beta
Hepatic stellate cells
A-SMase
alpha1 (I) procollagen
Investigación
Description
Summary: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.