Yiqi Yangyin Huazhuo Tongluo Formula alleviates diabetic podocyte injury by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy
10.12122/j.issn.1673-4254.2025.01.04
- VernacularTitle:益气养阴化浊通络方通过调控miR-21a-5p/FoxO1/PINK1介导的线粒体自噬减轻糖尿病肾病小鼠的足细胞损伤
- Author:
Kelei GUO
1
;
Yingli LI
;
Chenguang XUAN
;
Zijun HOU
;
Songshan YE
;
Linyun LI
;
Liping CHEN
;
Li HAN
;
Hua BIAN
Author Information
1. 南阳理工学院张仲景国医国药学院,河南 南阳 473004;南阳理工学院河南省张仲景方药与免疫调节重点实验室,河南 南阳 473004
- Publication Type:Journal Article
- Keywords:
diabetic nephropathy;
Yiqi Yangyin Huazhuo Tongluo Formula;
mitochondrial autophagy;
podocyte injury;
miR-21/FoxO1/PINK1
- From:
Journal of Southern Medical University
2025;45(1):27-34
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the protective effect of Yiqi Yangyin Huazhuo Tongluo Formula(YYHT)against high glucose-induced injury in mouse renal podocytes(MPC5 cells)and the possible mechanism.Methods Adult Wistar rats were treated with 19,38,and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose(30 mmol/L)prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic.The changes in miR-21a-5p expressions and the mRNA levels of FoxO1,PINK1,and Parkin in the treated cells were detected with qRT-PCR,and the protein levels of nephrin,podocin,FoxO1,PINK1,and Parkin were detected with Western blotting.Autophagic activity in the cells were evaluated with MDC staining.The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay.Results MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression,lowered expressions of FoxO1,PINK1,and Parkin1 mRNAs,and reduced levels of FoxO1,PINK1,parkin,nephrin,and podocin proteins and autophagic activity.Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin,inhibited the expression of miR-21a-5p,increased the mRNA and protein expressions of FoxO1,PINK1 and Parkin,and upregulated autophagic activity of the cells.Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells,and these effects were obviously attenuated by treatment with YYHT-medicated sera.Conclusion YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.
