کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8473634 | 1550392 | 2018 | 42 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
High phosphate-induced downregulation of PPARγ contributes to CKD-associated vascular calcification
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کلمات کلیدی
RGLRUNX2BMP-2PPARγHigh phosphatePiT1Mecp2SM22α - SM22achronic kidney disease - بیماری مزمن کلیویOsteogenic differentiation - تمایز OsteogenicBUN - خوبrosiglitazone - روزیگلیتازونRunt-related transcription factor 2 - عامل رونویسی مرتبط با روت 2CKD - نارسایی مزمن کلیهblood urea nitrogen - نیتروژن اوره خونperoxisome proliferator-activated receptor-gamma - پراکسیزوم پرولیفراتور فعال گیرنده گاماmethyl-CpG binding protein 2 - پروتئین متصل CpG متیل 2Vascular calcification - کلسیفیکاسیون عروقی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Medial arterial calcification associated with hyperphosphatemia is a main cause of cardiovascular mortality in patients with chronic kidney disease (CKD), but the mechanisms underlying high phosphate-induced vascular calcification remain largely unknown. Here, we observed a significant decrease in the expression of peroxisome proliferator-activated receptor-gamma (PPARγ) in calcified arteries both in CKD patients and in a mouse model of CKD with hyperphosphatemia. In vitro, high phosphate treatment led to a decreased expression of PPARγ in mouse vascular smooth muscle cells (VMSCs), accompanied by apparent osteogenic differentiation and calcification. Pretreatment with PPARγ agonist rosiglitazone significantly reversed high phosphate-induced VSMCs calcification. Further investigation showed that methyl-CpG binding protein 2 (Mecp2)-mediated epigenetic repression was involved in high phosphate-induced PPARγ downregulation. Moreover, the expression of Klotho that has the ability to inhibit vascular calcification by regulating phosphate uptake decreased with the PPARγ reduction in VSMCs after high phosphate treatment, and rosiglitazone failed to inhibit high phosphate-induced calcification in VSMCs with knockdown of Klotho or in aortic rings from Klotho-deficient (kl/kl) mice. Finally, an in vivo study demonstrated that oral administration of rosiglitazone could increase Klotho expression and protect against high phosphate-induced vascular calcification in CKD mice. These findings suggest that the inhibition of PPARγ expression may contribute to the pathogenesis of high phosphate-induced vascular calcification, which may provide a new therapeutic target for vascular calcification in CKD patients.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 114, January 2018, Pages 264-275
Journal: Journal of Molecular and Cellular Cardiology - Volume 114, January 2018, Pages 264-275
نویسندگان
Liang Liu, Yong Liu, Ying Zhang, Xianjin Bi, Ling Nie, Chi Liu, Jiachuan Xiong, Ting He, Xinlin Xu, Yanlin Yu, Ke Yang, Jun Gu, Yunjian Huang, Jingbo Zhang, Zhiren Zhang, Bo Zhang, Jinghong Zhao,