Metformin Alleviates Fibrosis of Trabecular Meshwork Cells Induced by TGFβ2 Through the Activation of Autophagy.

IF 2.3 4区医学 Q3 PHARMACOLOGY & PHARMACY

Dose-Response Pub Date : 2025-05-20 eCollection Date: 2025-04-01 DOI:10.1177/15593258251341598

Jing Ren, Pengtao Wu, Mengli Liu, Xuan Zhang, Zilu Guo, Yihan Liu, Rumeng Zhao, Gang Wang, Shichao Duan, Haijun Li

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引用次数: 0

Abstract

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.

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二甲双胍通过激活自噬减轻tgf - β2诱导的小梁网细胞纤维化

目的：本研究探讨二甲双胍对tgf - β2诱导的小梁网细胞纤维化的保护作用。方法：用tgf - β2或二甲双胍单独或联合处理转化的人小梁网细胞（HTMCs），采用免疫印迹法和免疫荧光染色法检测细胞自噬活性和纤维化蛋白表达水平。将tgf - β2或二甲双胍单独或联合注入小鼠眼前房。每周测定小鼠眼压（IOP），对小鼠眼切片进行免疫荧光染色，分析Col1、Col3的表达。pSmad3水平和定位评估TGFβ/Smad3通路活性。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htmc自噬，在体外和小鼠模型中有效改善tgf - β2诱导的tmc纤维化，降低tgf - β2引起的IOP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：本研究发现二甲双胍可减轻tgf - β2诱导的htmc纤维化，降低小鼠眼压升高。

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来源期刊

Dose-Response PHARMACOLOGY & PHARMACY-RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

CiteScore

4.90

自引率

4.00%

发文量

140

审稿时长

>12 weeks

期刊介绍： Dose-Response is an open access peer-reviewed online journal publishing original findings and commentaries on the occurrence of dose-response relationships across a broad range of disciplines. Particular interest focuses on experimental evidence providing mechanistic understanding of nonlinear dose-response relationships.