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
- Author:
Kelei GUO
1
;
Yingli LI
1
;
Chenguang XUAN
1
;
Zijun HOU
1
;
Songshan YE
1
;
Linyun LI
2
;
Liping CHEN
1
;
Li HAN
1
;
Hua BIAN
1
Author Information
1. ZHANG Zhongjing School of Chinese Medicine, Rheumatology and Immunology, Nanyang Traditional Chinese Medicine Hospital, Nanyang 473004, China.
2. Department of Nephrology, Rheumatology and Immunology, Nanyang Traditional Chinese Medicine Hospital, Nanyang 473004, China.
- Publication Type:Journal Article
- Keywords:
Yiqi Yangyin Huazhuo Tongluo Formula;
diabetic nephropathy;
miR-21/FoxO1/PINK1;
mitochondrial autophagy;
podocyte injury
- MeSH:
Animals;
MicroRNAs/genetics*;
Podocytes/pathology*;
Drugs, Chinese Herbal/pharmacology*;
Autophagy/drug effects*;
Rats, Wistar;
Protein Kinases/metabolism*;
Rats;
Forkhead Box Protein O1;
Mice;
Mitochondria/drug effects*;
Ubiquitin-Protein Ligases/metabolism*;
Glucose;
Diabetic Nephropathies;
Male;
Membrane Proteins/metabolism*;
Intracellular Signaling Peptides and Proteins
- From:
Journal of Southern Medical University
2025;45(1):27-34
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES: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.
CONCLUSIONS:YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.
