کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1940728 1050787 2006 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Aldosterone promotes fibronectin production through a Smad2-dependent TGF-β1 pathway in mesangial cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Aldosterone promotes fibronectin production through a Smad2-dependent TGF-β1 pathway in mesangial cells
چکیده انگلیسی

Accumulating evidence demonstrates that aldosterone can cause extra-cellular matrix (ECM) accumulation, in addition to regulating sodium and potassium homeostasis. Increased extra-cellular matrix production by renal glomerular mesangial cells has been suggested to be involved in pathogenesis of glomerular sclerosis. The present studies examine whether aldosterone is also produced in renal mesangial cells, and the effect of aldosterone on ECM accumulation in these cells. In cultured renal mesangial cells, aldosterone synthase (CYP11B2), mineralocorticoid receptor (MR), and 11β-HSD2 mRNA expressions were detected by RT-PCR. The ability of renal mesangial cells to produce aldosterone was confirmed by directly detecting aldosterone in culture medium via radioimmunoassay. Real-time RT-PCR showed that the expression of CYP11B2 mRNA in mesangial cells was significantly enhanced by AngII (P < 0.001) and by potassium (P < 0.05). Exposure of the cultured mesangial cells to aldosterone significantly increased fibronectin production from 12.4 ± 1.9 to 74.6 ± 16.8 ng/ml (P < 0.05). The aldosterone induced fibronectin production was abolished by aldosterone receptor antagonist spironolactone. Aldosterone also increased the TGF-β1 reporter luciferase activity from 0.8 ± 0.1 to 1.7 ± 0.1 (P < 0.05). Immunoblot showed TGF-β1 protein expression was increased following aldosterone treatment. Blocking TGF-β1 signaling pathway by knocking down Smad2 significantly blunted the aldosterone induced fibronectin production. The present studies indicate that renal mesangial cell is a target of local aldosterone action, which promotes ECM protein fibronectin production via TGF-β1/Smad2 signaling pathway.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 348, Issue 1, 15 September 2006, Pages 70–75
نویسندگان
, , , , ,