Effect of Dapagliflozin on cell proliferation,apoptosis and inflammation of podocytes induced by high glucose via regulating p38 MAPK pathway
10.3969/j.issn.1006-6187.2024.02.007
- VernacularTitle:达格列净调控p38丝裂原活化蛋白激酶通路对高糖诱导足细胞增殖、凋亡及炎症反应影响的研究
- Author:
Dong WANG
1
;
Juan LIU
;
Ruixiang DUAN
Author Information
1. 250000 济南,山东第一医科大学附属内分泌与代谢病医院内分泌科
- Keywords:
Diabetic kidney disease;
HGPC;
Dapagliflozin;
D-glucose;
p38 mitogen-activated protein kinase pathway;
Proliferation;
Apoptosis;
Infammation
- From:
Chinese Journal of Diabetes
2024;32(2):117-124
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of Dapagliflozin on high glucose-induced podocyte proliferation and apoptosis through p38 mitogen-activated protein kinase(p38 MAPK)pathway.Methods Human glomerular podocytes(HGPC)were divided into control(Con)group,low/medium/high D-glucose(Glu 10,Glu 20,Glu 30)group,high glucose(HG)group,low/medium/high concentration Dapagliflozin(HG+Dap 12.5,HG+Dap 25,HG+Dap 50)group,Dapagliflozin(HG+Dap)group,inhibitor(HG+ SB 203580)group,Dapagliflozin + inhibitor(HG+Dap+SB 203580)group and Dapagliflozin + activator(HG+Dap+C16-PAF)group.After 24 hours of intervention,the cell viability,proliferation rate,apoptosis rate and levels of related factors were tested.Results Compared with Con group,IL-1β,TNF-α,apoptosis rate,Caspase-3 mRNA and protein expression,p53,p-p38 MAPK protein expression were increased(P＜0.05),while cell proliferation rate,Cyclin D1 mRNA and protein expression were decreased in HG group(P＜0.05).Compared with HG group,the proliferation rate,Cyclin D1 mRNA and protein expression were increased(P＜0.05),while IL-1β,TNF-α,apoptosis rate,Caspase-3 mRNA and protein expression,p53,p-p38 MAPK protein expression were decreased in the HG+Dap and HG+SB 203580 groups(P＜0.05).Compared with HG+Dap group,cell proliferation rate,Cyclin D1 mRNA and protein expression were increased(P＜0.05),while IL-1β,TNF-α,apoptosis rate,Caspase-3 mRNA and protein expression,p53,p-p38 MAPK protein expression were decreased in HG+Dap+SB 203580 group(P＜0.05).In HG+Dap+C16-PAF group,IL-1β,TNF-α,apoptosis rate,Caspase-3 mRNA and protein expression,p53,p-p38 MAPK protein expression were increased(P＜0.05),while cell proliferation rate,Cyclin D1 mRNA and protein expression were decreased(P＜0.05).Conclusion Dagagliflozin can promote HGPC proliferation and inhibit apoptosis and inflammation in high D-glucose environment,and its mechanism may be related to the inhibition of p38 MAPK pathway signal transduction.
