3-Methyladenine alleviates extracellular matrix deposition in early diabetic nephropathy by inhibiting VEGF signaling
10.3760/cma.j.cn311282-20221130-00665
- VernacularTitle:3-甲基腺嘌呤抑制VEGF信号减轻早期糖尿病肾病细胞外基质沉积
- Author:
Benju LIU
1
;
Haiwen REN
;
Duo WANG
;
Jianhua CHEN
;
Qingyun LIU
;
Mingming PAN
;
Quan GONG
Author Information
1. 长江大学医学部，荆州 434023
- Keywords:
3-Methyladenine;
Diabetic nephropathy;
Extracellular matrix
- From:
Chinese Journal of Endocrinology and Metabolism
2023;39(10):876-881
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of 3-methyladenine(3-MA)on extracellular matrix deposition in early diabetic nephropathy(DN)and its mechanism.Methods:A streptozotocin(STZ)-induced type 1 diabetes mouse model was used, and the mice were divided into vehicle control group, diabetes group(STZ group), 3-MA group, and chloroquine(CQ)group, 8 mice in each group. After 6 weeks of intervention, both kidneys were harvested, and the kidney-to-body weight ratio was recorded. Western blotting was performed to detect protein expressions of renal cortex fibronectin, α-smooth muscle actin(α-SMA), LC3, Beclin 1, p62, and vascular endothelial growth factor(VEGF). Immunohistochemistry was used to observe kidney fibronectin staining. Bioinformatics analysis was conducted on shared genes between diabetic nephropathy(DN)gene targets and 3-MA predicted gene targets.Results:Both 3-MA and CQ exhibited certain hypoglycemic effects in diabetic mice. Compared to the STZ group, the kidney-to-body weight ratio decreased in the 3-MA group( P<0.05). Western blotting showed that 3-MA reduced the expression of renal cortex matrix-related proteins fibronectin and α-SMA in diabetic mice( P<0.05 or P<0.01). Immunohistochemistry also revealed that 3-MA reduced fibronectin staining in the kidneys of diabetic mice. Both 3-MA and CQ inhibited the protein expression of renal cortex Beclin 1 in diabetic mice(both P<0.05), while 3-MA increased the expression of renal cortex p62( P<0.05). Bioinformatics analysis indicated a connection between shared genes of DN gene targets and 3-MA predicted gene targets with the VEGF signaling pathway. Western blotting results further showed that 3-MA reduced renal cortex VEGF expression in diabetic mice( P<0.01). Conclusion:3-MA can alleviate extracellular matrix deposition in the kidneys of early DN mice by inhibiting the VEGF signaling pathway.
