کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5689012 | 1409967 | 2017 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Rhein reverses Klotho repression via promoter demethylation and protects against kidney and bone injuries in mice with chronic kidney disease
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای کلیوی
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چکیده انگلیسی
Rhein is an anthraquinone compound isolated from the medicinal plant rhubarb and mainly used in the clinical treatment of diabetic nephropathy. Rhein exhibits various renoprotective functions, but the underlying mechanisms are not fully determined. However, its renoprotective properties recapitulate the role of Klotho, a renal-specific antiaging protein critical for maintaining kidney homeostasis. Here we explored the connections between rhein renoprotection and Klotho in a mouse model of adenine-induced chronic kidney disease. In addition to being an impressive Klotho upregulator, rhein remarkably reversed renal Klotho deficiency in adenine-treated mice. This effect was associated with significant improvement in disturbed serum biochemistry, profibrogenic protein expression, and kidney and bone damage. Further investigation of the molecular basis of Klotho loss revealed that these kidneys displayed marked inductions of DNA methyltransferase DNMT1/DNMT3a and Klotho promoter hypermethylation, whereas rhein treatment effectively corrected these alterations. The renal protective effects of rhein were largely abolished when Klotho was knocked-down by RNA interferences, suggesting that rhein reversal of Klotho deficiency is essential for its renoprotective actions. Thus, our study clarifies how rhein regulation of Klotho expression contributes to its renoprotection and brings new insights into Klotho-targeted strategy for the treatment of kidney diseases of various etiologies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 91, Issue 1, January 2017, Pages 144-156
Journal: Kidney International - Volume 91, Issue 1, January 2017, Pages 144-156
نویسندگان
Qin Zhang, Lin Liu, Wenjun Lin, Shasha Yin, Aiping Duan, Zhihong Liu, Wangsen Cao,