We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
TGF-beta1 activates MAP kinase in human mesangial cells: a possible role in collagen expression.
- Authors
Hayashida, T; Poncelet, A C; Hubchak, S C; Schnaper, H W
- Abstract
<bold>Background: </bold>Although the pathogenic relevance of transforming growth factor-beta (TGF-beta) to glomerular sclerosis has been established, the intracellular mechanisms by which TGF-beta induces extracellular matrix accumulation are not fully understood. We examined whether the mitogen-activated protein (MAP) kinase pathway is involved in TGF-beta1-induced collagen expression by cultured human mesangial cells.<bold>Methods: </bold>The activation of MAP kinase pathways by TGF-beta1 was assessed by immunoblot with anti-phospho-ERK or -JNK antibodies and by transfection of plasmids expressing pathway-specific transcription activators fused to the DNA-binding domain of GAL4, as well as a GAL4 response element-luciferase reporter gene. The role of MAP kinase was assessed using biochemical inhibitors and transiently expressed dominant negative mutant constructs. The effects on TGF-beta1-induced alpha1(I) collagen expression were evaluated by Northern blot and by activation of a transiently transfected alpha1(I) promoter-luciferase reporter construct.<bold>Results: </bold>ERK and JNK phosphorylation occurred 30 minutes and one hour, respectively, after TGF-beta1 treatment. A biochemical blockade of the ERK pathway inhibited TGF-beta1-induced alpha1(I) collagen expression. A dominant negative mutant of ERK1 but not of JNK decreased alpha1(I) gene promoter activation. Activation of the TGF-beta-responsive p3TP-Lux construct was partially inhibited by cotransfection of an ERK1 dominant negative mutant.<bold>Conclusion: </bold>These data indicate that MAP kinase pathways can be activated by TGF-beta1 in mesangial cells and that the ERK MAP kinase plays a role in TGF-beta-stimulated collagen I expression. Because we have shown previously that SMADs mediate TGF-beta1-stimulated collagen I expression, our findings raise the possibility of interactions between the MAP kinase and the SMAD pathways.
- Subjects
BIOCHEMISTRY; CARRIER proteins; CELL culture; COLLAGEN; COMPARATIVE studies; GROWTH factors; KIDNEY glomerulus; PHENOMENOLOGY; RESEARCH methodology; MEDICAL cooperation; PROTEINS; RESEARCH; TRANSFERASES; DNA-binding proteins; EVALUATION research
- Publication
Kidney International, 1999, Vol 56, Issue 5, p1710
- ISSN
0085-2538
- Publication type
journal article
- DOI
10.1046/j.1523-1755.1999.00733.x