3-Methyladenine alleviates early renal injury in diabetic mice by inhibiting AKT signaling
10.12122/j.issn.1673-4254.2024.07.03
- VernacularTitle:3-甲基腺嘌呤通过抑制AKT信号减轻糖尿病小鼠的早期肾损伤
- Author:
Benju LIU
1
;
Yelei WANG
;
Haiwen REN
;
Liwen OU
;
Xuan DENG
;
Mengxin HUANG
;
Xin WU
;
Quan GONG
Author Information
1. 长江大学医学部人体解剖学教研室,湖北 荆州 434023
- Keywords:
3-methyladenine;
diabetic kidney disease;
mesangial cells;
renal injury
- From:
Journal of Southern Medical University
2024;44(7):1236-1242
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism of 3-methyladenine(3-MA)for alleviating early diabetic renal injury.Methods Mouse models of streptozotocin(STZ)-induced diabetes mellitus were randomized into model group and 3-MA treatment group for daily treatments with normal saline and 10 mg/kg 3-MA by gavage for 6 weeks,respectively.Body weight and fasting blood glucose of the mice were recorded every week.After the treatments,the kidneys of the mice were collected for measurement kidney/body weight ratio,examination of glomerular size with PAS staining,and detection of α-SMA and PCNA expressions using Western blotting and immunohistochemistry.SV40 MES 13 cells cultured in normal glucose(5.6 mmol/L)and high glucose(30 mmol/L)were treated with 24.4 mmol/L mannitol and 5 mmol/L 3-MA for 24 h,respectively,and the changes in cell viability and PCNA expression were examined using CCK8 assay and Western blotting.Bioinformatics analysis of the intersecting gene targets of diabetic kidney disease(DKD)and 3-MA was performed,and the results were verified by Western blotting both in vivo and in vitro.Results In the diabetic mice,treatment with 3-MA produced a short-term hypoglycemic effect,reduced the kidney/body weight ratio and glomerular hypertrophy,and decreased the expressions of α-SMA and PCNA in the renal cortex.In the in vitro study,3-MA significantly lowered the viability and reduced PCNA expression in SV40 MES 13 cells exposed to high glucose.The results of bioinformatic analysis identified AKT1 as the key gene in the therapeutic mechanism of 3-MA for DKD.Western blotting confirmed that 3-MA inhibited the phosphorylation of AKT and S6 in both the renal cortex of diabetic mice and high glucose-treated SV40 MES 13 cells.Conclusion 3-MA suppresses mesangial cell proliferation and alleviates early diabetic renal injury in mice possibly by inhibiting AKT signaling.
