کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5688292 | 1409897 | 2017 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Murine recombinant angiotensin-converting enzyme 2 attenuates kidney injury in experimental Alport syndrome
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای کلیوی
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چکیده انگلیسی
Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase in the renin-angiotensin system that catalyzes the breakdown of angiotensin II to angiotensin 1-7. We have reported that ACE2 expression in the kidney is reduced in experimental Alport syndrome but the impact of this finding on disease progression has not been studied. Accordingly, we evaluated effects of murine recombinant ACE2 treatment in Col4a3 knockout mice, a model of Alport syndrome characterized by proteinuria and progressive renal injury. Murine recombinant ACE2 (0.5 mg/kg/day) was administered from four to seven weeks of age via osmotic mini-pump. Pathological changes were attenuated by murine recombinant ACE2 treatment which ameliorated kidney fibrosis as shown by decreased expression of COL1α1 mRNA, less accumulation of extracellular matrix proteins, and inhibition of transforming growth factor-β signaling. Further, increases in proinflammatory cytokine expression, macrophage infiltration, inflammatory signaling pathway activation, and heme oxygenase-1 levels in Col4a3 knockout mice were also reduced by murine recombinant ACE2 treatment. Lastly, murine recombinant ACE2 influenced the turnover of renal ACE2, as it suppressed the expression of tumor necrosis factor-α converting enzyme, a negative regulator of ACE2. Thus, treatment with exogenous ACE2 alters angiotensin peptide metabolism in the kidneys of Col4a3 knockout mice and attenuates the progression of Alport syndrome nephropathy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 91, Issue 6, June 2017, Pages 1347-1361
Journal: Kidney International - Volume 91, Issue 6, June 2017, Pages 1347-1361
نویسندگان
Eun Hui Bae, Fei Fang, Vanessa R. Williams, Ana Konvalinka, Xiaohua Zhou, Vaibhav B. Patel, Xuewen Song, Rohan John, Gavin Y. Oudit, York Pei, James W. Scholey,