Roscovitine attenuates renal interstitial fibrosis in diabetic mice through the TGF-beta 1/p38 MAPK pathway
Roscovitine attenuates renal interstitial fibrosis in diabetic mice through the TGF-beta 1/p38 MAPK pathway
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Roscovitine 通过 TGF-β 1/p38 MAPK 途径减轻糖尿病小鼠的肾间质纤维化
DOI：
10.1016/j.biopha.2019.108895
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发表时间：
2019
影响因子：
7.5
通讯作者：
Liu Wei
中科院分区：
文献类型：
--
作者：
Wang Shuo;Zhou Yi;Zhang Yue;He Xingyu;Zhao Xiangning;Zhao Hairong;Liu Wei
肾小管间质纤维化是糖尿病肾病的标志，糖尿病肾病是全球终末期肾病的主要原因。Roscovitine是Cdks的抑制剂，具有抗纤维化作用。本研究旨在探讨Roscovitine对糖尿病肾病肾纤维化的保护作用。体内研究表明，roscovitine治疗显着改善糖尿病小鼠肾功能和组织学损伤。Roscovitine可协同抑制胶原、α-SMA、TGF-β1的表达，并保留E-cadherin的表达。在细胞水平，roscovitine处理高糖培养的HK 2细胞。结果表明，roscovitine可有效降低肾小管上皮细胞EMT的标志物--α-SMA的表达，并改善其表达水平的下降。在分子水平上，roscovitine通过抑制高糖培养的HK 2细胞中TGF-β1/p38 MAPK通路的上调而发挥这种作用。这些研究表明roscovitine通过抑制TGF-β1/p38 MAPK通路发挥抗糖尿病小鼠肝纤维化作用。
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, α-SMA, TGF-β1, and retaining E-cadherin expression. At the cellular level, roscovitine treated HK2 cells cultured with high glucose. It was revealed that roscovitine successfully reduced α-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-β1/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-β1/p38MAPK pathway in diabetic mice.