کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6163391 | 1249431 | 2015 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mammalian target of rapamycin signaling inhibition ameliorates vascular calcification via Klotho upregulation
ترجمه فارسی عنوان
هدف قرار دادن پستانداران مهار رگامایسین سیگنالینگ باعث کاهش کلسیفیکاسیون عروقی از طریق تقویت کلوتو می شود
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کلمات کلیدی
سالخورده، نارسایی مزمن کلیه، فسفات معدنی، سلول عضله صاف عروقی،
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای کلیوی
چکیده انگلیسی
Vascular calcification (VC) is a major risk factor for cardiovascular mortality in chronic renal failure (CRF) patients, but the pathogenesis remains partially unknown and effective therapeutic targets should be urgently explored. Here we pursued the therapeutic role of rapamycin in CRF-related VC. Mammalian target of rapamycin (mTOR) signal was activated in the aortic wall of CRF rats. As expected, oral rapamycin administration significantly reduced VC by inhibiting mTOR in rats with CRF. Further in vitro results showed that activation of mTOR by both pharmacological agent and genetic method promoted, while inhibition of mTOR reduced, inorganic phosphate-induced vascular smooth muscle cell (VSMC) calcification and chondrogenic/osteogenic gene expression, which were independent of autophagy and apoptosis. Interestingly, the expression of Klotho, an antiaging gene that suppresses VC, was reduced in calcified vasculature, whereas rapamycin reversed membrane and secreted Klotho decline through mTOR inhibition. When mTOR signaling was enhanced by either mTOR overexpression or deletion of tuberous sclerosis 1, Klotho mRNA was further decreased in phosphate-treated VSMCs, suggesting a vital association between mTOR signaling and Klotho expression. More importantly, rapamycin failed to reduce VC in the absence of Klotho by using either siRNA knockdown of Klotho or Klotho knockout mice. Thus, Klotho has a critical role in mediating the observed decrease in calcification by rapamycin in vitro and in vivo.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 88, Issue 4, October 2015, Pages 711-721
Journal: Kidney International - Volume 88, Issue 4, October 2015, Pages 711-721
نویسندگان
Yang Zhao, Ming-Ming Zhao, Yan Cai, Ming-Fei Zheng, Wei-Liang Sun, Song-Yang Zhang, Wei Kong, Jun Gu, Xian Wang, Ming-Jiang Xu,