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

Montiel-Duarte, C²  Jaffrèzou, J.P¹  Osés-Prieto, J.A²  Rojkind, M³  López-Zabalza, M.J²  Iraburu, M.J²  Varela-Rey, M² 

[1] INSERM E9910, Institut Claudius Régaud, 31052 Toulouse, France;Department of Biochemistry, University of Navarra, C/Irunlarrea 1, 31008 Pamplona, Spain;Department of Clinical Investigation, Walter Reed Army Medical Center, 6900 Georgia Avenue NW, Washington, DC 20307, USA

关键词: p38 MAPK;    TNF-α;    TGF-β;    Hepatic stellate cells;    A-SMase;    α1(I) procollagen;    TNF-α;    tumor necrosis factor α;    TGF-β;    transforming growth factor β;    HSC;    hepatic stellate cells;    col1a1;    α1(I) procollagen;    ERK;    extracellular-regulated kinase;    JNK;    Jun-N-terminal kinase;    MAPK;    mitogen-activated protein kinase;    A-SMase;    acidic sphingomyelinase;    N-SMase;    neutral sphingomyelinase;   

DOI  :  10.1016/S0014-5793(02)03276-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The role of members of the mitogen-activated protein kinase (MAPK) family on tumor necrosis factor α (TNF-α)-mediated down-regulation of col1a1 gene was studied. TNF-α increased extracellular-regulated kinase and Jun-N-terminal kinase phosphorylation, but these effects were not related to its inhibitory effect on α1(I) procollagen (col1a1) mRNA levels. Phosphorylation of p38 MAPK was decreased in response to TNF-α, and the specific p38 MAPK inhibitor SB203580 mimicked the effect of TNF-α on col1a1 mRNA levels. Transforming growth factor β (TGF-β) increased p38 MAPK phosphorylation and SB203580 prevented the induction of col1a1 mRNA levels by TGF-β. These results suggest that p38 MAPK plays an important role in regulating the expression of col1a1 in hepatic stellate cells in response to cytokines.

【 授权许可】

Unknown