Rodriguez-Barbero, A. and Dorado, F. and Velasco, S. and Pandiella, A. and Banas, B. and Lopez-Novoa, J. M. (2006) TGF-beta 1 induces COX-2 expression and PGE(2) synthesis through MAPK and PI3K pathways in human mesangial cells. KIDNEY INTERNATIONAL, 70 (5). pp. 901-909. ISSN 0085-2538, 1523-1755
Full text not available from this repository. (Request a copy)Abstract
Transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1, and COX-2 expression can be induced in MC. However, to date, there are no published data on the possible role of TGF-beta 1 in COX-2 expression in human mesangial cells (HMC). We designed studies to determine (1) whether TGF-beta 1 stimulates COX-2 expression in primary HMC, (2) whether mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) cascades are involved in TGF-beta 1-induced COX-2 expression, and (3) whether prostaglandin (PG)E-2 synthesis is affected by TGF-beta 1 and MAP kinases and PI3K activation. Studies were performed in primary cultures of HMC and in an immortalized line of HMC. TGF-beta 1 induces COX-2 promoter activity and COX-2 mRNA and protein expression in HMC. COX-2 induction is accompanied by increased PGE(2) synthesis. Extracellular signal-regulated kinase (ERK)1/2, p38 MAPK, and PI3K pathway inhibition blunted TGF-beta 1-induced COX-2 overexpression. We demonstrate that TGF-beta 1 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INTESTINAL EPITHELIAL-CELLS; PROTEIN-KINASE CASCADES; MESSENGER-RNA STABILITY; SMOOTH-MUSCLE-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; CYCLOOXYGENASE-2 EXPRESSION; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; UP-REGULATION; CANCER-CELLS; transforming growth factor-beta 1; cyclooxygenase; prostaglandin-E-2; mesangial cells; mitogen-activated protein kinase; phosphatidylinositol 3 kinase |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Feb 2021 07:12 |
| Last Modified: | 03 Feb 2021 07:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/34119 |
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