Metformin attenuates renal tubulointerstitial fibrosis via upgrading autophagy in the early stage of diabetic nephropathy.
Metformin attenuates renal tubulointerstitial fibrosis via upgrading autophagy in the early stage of diabetic nephropathy.
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二甲双胍通过增强糖尿病肾病早期自噬来减轻肾小管间质纤维化
DOI：
10.1038/s41598-021-95827-5
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发表时间：
2021-08-11
影响因子：
4.6
通讯作者：
Sun D
中科院分区：
文献类型：
--
作者：
Wang F;Sun H;Zuo B;Shi K;Zhang X;Zhang C;Sun D
本研究旨在比较体内二甲双胍对糖尿病肾病（DN）不同阶段肾小管间质纤维化（TIF）的影响，并在体外评价高糖（HG）处理的肾小管上皮细胞（RTECs）的机制。采用Sprague-Dawley（SD）大鼠建立DN模型，测定各项生化指标及体重变化。采用组织学分析、免疫组织化学和免疫印迹法定量肾纤维化程度。研究自噬与糖尿病肾病之间的潜在关系，以及二甲双胍对上皮细胞向间质细胞转化（EMT）的细胞调控机制。二甲双胍显著改善肾功能和肾组织的组织学恢复，特别是在DN的早期阶段，自噬显著增加，肾组织中纤维化生物标志物（纤连蛋白和胶原I）的表达降低。在高血糖条件下，肾小管上皮细胞失活p-AMPK和激活部分EMT。二甲双胍诱导的AMPK可明显改善肾脏自噬功能，抑制RTECs部分EMT，减少TIF，有效预防或延缓DN的发生。这一证据为后续研究二甲双胍治疗糖尿病TIF的潜在临床应用提供了理论和实验依据。
This study aimed at comparing the effects of metformin on tubulointerstitial fibrosis (TIF) in different stages of diabetic nephropathy (DN) in vivo and evaluating the mechanism in high glucose (HG)-treated renal tubular epithelial cells (RTECs) in vitro. Sprague–Dawley (SD) rats were used to establish a model of DN, and the changes of biochemical indicators and body weight were measured. The degree of renal fibrosis was quantified using histological analysis, immunohistochemistry, and immunoblot. The underlying relationship between autophagy and DN, and the cellular regulatory mechanism of metformin on epithelial-to-mesenchymal transition (EMT) were investigated. Metformin markedly improved renal function and histological restoration of renal tissues, especially in the early stages of DN, with a significant increase in autophagy and a decrease in the expression of fibrotic biomarkers (fibronectin and collagen I) in renal tissue. Under hyperglycemic conditions, renal tubular epithelial cells inactivated p-AMPK and activated partial EMT. Metformin-induced AMPK significantly ameliorated renal autophagic function, inhibited the partial EMT of RTECs, and attenuated TIF, all of which effectively prevented or delayed the onset of DN. This evidence provides theoretical and experimental basis for the following research on the potential clinical application of metformin in the treatment of diabetic TIF.
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影响因子：
7.3
作者：
Gonzalez DM;Medici D
通讯作者：
Medici D
影响因子：
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作者：
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通讯作者：
Fan, Zhongyi
影响因子：
2
作者：
Cao, Tao;Xu, Ricong;Wan, Qijun
通讯作者：
Wan, Qijun
影响因子：
4.7
作者：
Kang, Min-Kyung;Park, Sin-Hye;Kang, Young-Hee
通讯作者：
Kang, Young-Hee
表观遗传上调的癌蛋白 PLCE1 通过激活 PI-PLC epsilon-NF-B 信号通路和 VEGF-C/Bcl-2 表达来驱动食管癌血管生成和增殖
影响因子：
37.3
作者：
Chen, Yunzhao;Wang, Dandan;Li, Feng
通讯作者：
Li, Feng