二甲双胍通过激活自噬减轻转化生长因子β2诱导的小梁网细胞纤维化。
Metformin Alleviates Fibrosis of Trabecular Meshwork Cells Induced by TGFβ2 Through the Activation of Autophagy.
作者信息
Ren Jing, Wu Pengtao, Liu Mengli, Zhang Xuan, Guo Zilu, Liu Yihan, Zhao Rumeng, Wang Gang, Duan Shichao, Li Haijun
机构信息
Henan Provincial People's Hospital, Henan Eye Hospital, Henan Eye Institute, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, China.
Department of neurology, The First People's Hospital of Zhengzhou, Zhengzhou, China.
出版信息
Dose Response. 2025 May 20;23(2):15593258251341598. doi: 10.1177/15593258251341598. eCollection 2025 Apr-Jun.
OBJECTIVE
In this study, we investigated the protective effect of Metformin on fibrosis of trabecular meshwork cells induced by TGFβ2.
METHODS
Transformed and primary human trabecular meshwork cells (HTMCs) were treated with TGFβ2 or Metformin alone or combination, western blotting and immunofluorescence staining assays to detect autophagy activity and fibrotic proteins expression levels. TGFβ2 or Metformin alone or combination were injected into the anterior chamber of mouse eye. Mouse intraocular pressure (IOP) was measured every week, mouse eye sections were conducted immunofluorescence staining to analyze Col1 and Col3 expression. pSmad3 level and localization to evaluate TGFβ/Smad3 pathway activity. Chloroquine phosphate was used to block autophagy-lysosome pathway.
RESULTS
Metformin activates autophagy of HTMCs in a dose dependent manner and efficiently ameliorates TMCs fibrosis induced by TGFβ2 in vitro and in mouse model, and decreased elevated IOP caused by TGFβ2. Metformin promotes fibrotic proteins degradation through the autophagy-lysosome pathway.
CONCLUSION
Our study found Metformin could alleviates fibrosis of HTMCs induced by TGFβ2 and decreased elevated IOP in mouse model.
目的
在本研究中，我们调查了二甲双胍对转化生长因子β2（TGFβ2）诱导的小梁网细胞纤维化的保护作用。
方法
将转化的和原代人小梁网细胞（HTMCs）单独或联合用TGFβ2或二甲双胍处理，采用蛋白质免疫印迹法和免疫荧光染色法检测自噬活性和纤维化蛋白表达水平。将TGFβ2或二甲双胍单独或联合注射到小鼠眼前房。每周测量小鼠眼压，对小鼠眼切片进行免疫荧光染色以分析Ⅰ型胶原（Col1）和Ⅲ型胶原（Col3）的表达。检测磷酸化Smad3（pSmad3）水平和定位以评估TGFβ/Smad3信号通路活性。使用磷酸氯喹阻断自噬-溶酶体途径。
结果
二甲双胍以剂量依赖的方式激活HTMCs的自噬，并在体外和小鼠模型中有效改善TGFβ2诱导的TMCs纤维化，并降低由TGFβ2引起的眼压升高。二甲双胍通过自噬-溶酶体途径促进纤维化蛋白降解。
结论
我们的研究发现二甲双胍可以减轻TGFβ2诱导的HTMCs纤维化，并降低小鼠模型中的眼压升高。
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