Rodríguez-Barbero, A. and Dorado, F. and Velasco, S. and Pandiella, A. and Banas, B. and López-Novoa, J. M. (2006) TGF-beta1 induces COX-2 expression and PGE2 synthesis through MAPK and PI3K pathways in human mesangial cells. Kidney international 70 (5), pp. 901-909.
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Other URL: http://dx.doi.org/10.1038/sj.ki.5001626
Transforming growth factor-beta1 (TGF-beta1) plays a fundamental role in the progression of renal diseases. Accumulating evidence has suggested that eicosanoids derived from cyclooxygenase-2 (COX-2) participate in a number of pathological processes in immune-mediated renal diseases. Mesangial cells (MC) play a major role in physiological and pathophysiological renal processes. MC express receptors for TGF-beta1, and COX-2 expression can be induced in MC. However, to date, there are no published data on the possible role of TGF-beta1 in COX-2 expression in human mesangial cells (HMC). We designed studies to determine (1) whether TGF-beta1 stimulates COX-2 expression in primary HMC, (2) whether mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) cascades are involved in TGF-beta1-induced COX-2 expression, and (3) whether prostaglandin (PG)E2 synthesis is affected by TGF-beta1 and MAP kinases and PI3K activation. Studies were performed in primary cultures of HMC and in an immortalized line of HMC. TGF-beta1 induces COX-2 promoter activity and COX-2 mRNA and protein expression in HMC. COX-2 induction is accompanied by increased PGE2 synthesis. Extracellular signal-regulated kinase (ERK)1/2, p38 MAPK, and PI3K pathway inhibition blunted TGF-beta1-induced COX-2 overexpression. We demonstrate that TGF-beta1 regulates COX-2 expression in HMC through the activation of ERK1/2, p38 MAPK, and PI3K. These results can help to elucidate the molecular mechanisms underlying the regulation of COX-2 and open up specific strategies for the treatment of glomerular disease.
|Institutions:||Medicine > Lehrstuhl für Innere Medizin II|
|Keywords:||transforming growth factor-1; cyclooxygenase; prostaglandin-E2; mesangial cells; mitogen-activated protein kinase; phosphatidylinositol 3 kinase|
|Subjects:||600 Technology > 610 Medical sciences Medicine|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Yes|
|Deposited On:||22 Mar 2007|
|Last Modified:||20 Jul 2011 20:54|