کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5939750 1573484 2006 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Regular ArticlesA Possible Anti-Inflammatory Role of Angiotensin II Type 2 Receptor in Immune-Mediated Glomerulonephritis during Type 1 Receptor Blockade
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Regular ArticlesA Possible Anti-Inflammatory Role of Angiotensin II Type 2 Receptor in Immune-Mediated Glomerulonephritis during Type 1 Receptor Blockade
چکیده انگلیسی

We previously reported that angiotensin II type 1 receptor (AT1R) blockade attenuates renal inflammation/fibrogenesis in immune-mediated glomerulonephritis via angiotensin II type 2 receptor (AT2R). In the present study, further in vivo experiments revealed that AT2R was expressed in tubular epithelial cells of nephritic kidneys in mice, and feedback activation of the renin-angiotensin system during AT1R blockade significantly reduced p-ERK, but not intranuclear nuclear factor-κB, levels via AT2R. This led to reduction in mRNA levels of the proinflammatory mediator monocyte chemoattractant protein-1 and overall interstitial inflammation and subsequent fibrogenesis. Specific blockade of ERK expression in tubular epithelium by anti-sense oligodeoxynucleotides also attenuated interstitial inflammation, mimicking the anti-inflammatory action of AT2R in nephritic kidneys. Alternatively, we succeeded in confirming such an AT2R function by demonstrating that AT1R blockade did not confer renoprotection in nephritic, AT2R gene-deficient mice. Additional in vitro experiments revealed that AT2R activation did not affect nuclear factor-κB activation by tumor necrosis factor-α in cultured tubular epithelial cells, although it inhibited ERK phosphorylation, which reduced monocyte chemoattractant protein-1 mRNA levels. These results suggest that feedback activation of AT2Rs in tubular epithelium of nephritic kidneys plays an important role in attenuating interstitial inflammation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The American Journal of Pathology - Volume 169, Issue 5, November 2006, Pages 1577-1589
نویسندگان
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