Roscovitine attenuates renal interstitial fibrosis in diabetic mice through the TGF-β1/p38 MAPK pathway

被引：37
作者：
Wang, Shuo [1 ,2 ]
Zhou, Yi [3 ]
Zhang, Yue [4 ]
He, Xingyu [1 ,2 ]
Zhao, Xiangning [1 ,2 ]
Zhao, Hairong [1 ,2 ]
Liu, Wei [1 ,2 ]
机构：
[1] Hebei Med Univ, Dept Pathol, 361 Zhongshan East Rd, Shijiazhuang 050017, Hebei, Peoples R China
[2] Hebei Med Univ, Key Lab Kidney Dis Hebei Prov, 361 Zhongshan East Rd, Shijiazhuang 050017, Hebei, Peoples R China
[3] Hebei Med Univ, Hosp 2, Dept Neurol, Shijiazhuang 050000, Hebei, Peoples R China
[4] Hebei Med Univ, Dept Diagnost, Shijiazhuang 050017, Hebei, Peoples R China
来源：
BIOMEDICINE & PHARMACOTHERAPY | 2019年 / 115卷
基金：
中国博士后科学基金; 中国国家自然科学基金;
关键词：
Diabetic nephropathy; Tubulointerstitial fibrosis; Roscovitine; TGF-beta; 1; p38; MAPK; CYCLIN-DEPENDENT KINASE-5; TUBULAR CELLS; TGF-BETA; C-JUN; INHIBITION; PATHOPHYSIOLOGY; ACTIVATION; PROTECTS;
D O I：
10.1016/j.biopha.2019.108895
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Tubulointerstitial fibrosis is the hallmark of diabetic nephropathy, which is the leading cause of end-stage renal disease worldwide. Roscovitine, an inhibitor of Cdks, exhibits anti-fibrosis effects. The present study was aimed to explore the protected role of roscovitine from renal fibrosis of diabetic nephropathy. In vivo study showed that roscovitine treatment significantly ameliorated renal functional and histological injuries in diabetic mice. It was also showed that roscovitine coordinately inhibited the expression of collagen, alpha-SMA, TGF-beta 1, and retaining E-cadherin expression. At the cellular level, roscovitine treated HK2 cells cultured with high glucose. It was revealed that roscovitine successfully reduced alpha-SMA expression and ameliorated the decrease expression of E-cadherin, the two markers of tubular cell EMT. At the molecular level, roscovitine was found to exert this effect through inhibiting the up-regulation of TGF-beta 1/p38MAPK pathway in high glucose cultured HK2 cells. These study demonstrated a novel mechanism that roscovitine has the anti-fibrosis effects by inhibiting the TGF-beta 1/ p38MAPK pathway in diabetic mice.
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页数：7
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