کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5502041 | 1534935 | 2017 | 50 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
WT1 ameliorates podocyte injury via repression of EZH2/β-catenin pathway in diabetic nephropathy
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کلمات کلیدی
CCReGFP2′, 7′-dichlorodihydrofluorescein diacetateCTNNB1DCFH-DADAPIEGFREZH24,6-diamidino-2-phenylindole - 4،6-دیامیدین-2-فنیلینولDMSO - DMSOchromatin immunoprecipitation - ایمن سازی کروماتینBUN - خوبdimethyl sulphoxide - دی متیل سولفوکسیدCreatinine clearance rate - میزان ترخیص کراتینینestimated glomerular filtration rate - میزان تصفیه گلومرولی برآورد شده استDiabetic nephropathy - نفروپاتی دیابتیblood urea nitrogen - نیتروژن اوره خونenhanced green fluorescence protein - پروتئین فلورسانس سبز افزایش یافته استCHiP - چیپ
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Epigenetic modulation of podocyte injury plays a pivotal role in diabetic nephropathy (DN). Wilm's tumor 1 (WT1) has been found to have opposing roles with β-catenin in podocyte biology. Herein, we asked whether the histone methyltransferase enzyme enhancer of zeste homolog 2 (EZH2) promotes WT1-induced podocyte injury via β-catenin activation and the underlying mechanisms. We found that WT1 antagonized EZH2 and ameliorated β-catenin-mediated podocyte injury as demonstrated by attenuated podocyte mesenchymal transition, maintenance of podocyte architectural integrity, decreased podocyte apoptosis and oxidative stress. Further, we provided mechanistical evidence that EZH2 was required in WT1-mediated β-catenin inactivation via repression of secreted frizzled-related protein 1 (SFRP-1), a Wnt antagonist. Moreover, EZH2-mediated silencing of SFRP-1 was due to increased histone 3 lysine 27 trimethylation (H3K27me3) on its promoter region. WT1 favored renal function and decreased podocyte injury in diabetic rats and DN patients. Notably, WT1 exhibited clinical and biological relevance as it was linked to dropped serum creatinine, decreased proteinuria and elevated estimated glomerular filtration rate (eGFR). We propose an epigenetic process via the WT1/EZH2/β-catenin axis in attenuating podocyte injury in DN. Targeting WT1 and EZH2 could be potential therapeutic approaches for DN.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 108, July 2017, Pages 280-299
Journal: Free Radical Biology and Medicine - Volume 108, July 2017, Pages 280-299
نویسندگان
Jiao Wan, Xiaoyan Hou, Zhanmei Zhou, Jian Geng, Jianwei Tian, Xiaoyan Bai, Jing Nie,