کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3889619 1249668 2006 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
TGF-β1 induces COX-2 expression and PGE2 synthesis through MAPK and PI3K pathways in human mesangial cells
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های کلیوی
پیش نمایش صفحه اول مقاله
TGF-β1 induces COX-2 expression and PGE2 synthesis through MAPK and PI3K pathways in human mesangial cells
چکیده انگلیسی

Transforming growth factor-β1 (TGF-β1) 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-β1, and COX-2 expression can be induced in MC. However, to date, there are no published data on the possible role of TGF-β1 in COX-2 expression in human mesangial cells (HMC). We designed studies to determine (1) whether TGF-β1 stimulates COX-2 expression in primary HMC, (2) whether mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) cascades are involved in TGF-β1-induced COX-2 expression, and (3) whether prostaglandin (PG)E2 synthesis is affected by TGF-β1 and MAP kinases and PI3K activation. Studies were performed in primary cultures of HMC and in an immortalized line of HMC. TGF-β1 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-β1-induced COX-2 overexpression. We demonstrate that TGF-β1 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 70, Issue 5, 1 September 2006, Pages 901–909
نویسندگان
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