RESUMO
BACKGROUND: Ginsenoside Rg3 is an active saponin isolated from ginseng, which can reduce renal inflammation. However, the role and mechanism of Rg3 in diabetic kidney disease (DKD) are far from being studied. METHODS: The effects of Rg3 and miR-216a-5p on the proliferation, apoptosis, and MAPK pathway in high glucose (HG)-induced SV40 MES 13 were monitored by CCK-8, TUNEL staining, and western blot. RESULTS: Rg3 treatment could accelerate proliferation and suppress apoptosis in HG-induced SV40 MES. Moreover, miR-216a-5p inhibition also could alleviate renal injury, prevent apoptosis, and activate the MAPK pathway in kidney tissues of diabetic model mice. CONCLUSION: Rg3 could attenuate DKD progression by downregulating miR-216a-5p, suggesting Rg3 and miR-216a-5p might be the potential drug and molecular targets for DKD therapy.
Assuntos
Apoptose , Proliferação de Células , Diabetes Mellitus Experimental , Nefropatias Diabéticas , Ginsenosídeos , Sistema de Sinalização das MAP Quinases , Células Mesangiais , MicroRNAs , Ginsenosídeos/farmacologia , MicroRNAs/metabolismo , MicroRNAs/genética , Animais , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Camundongos , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Masculino , Linhagem CelularRESUMO
AIMS/INTRODUCTION: Glucose metabolic disorder is the main cause for type 2 diabetes progression. Exploring the molecular mechanisms of metabolic disorder are crucial for type 2 diabetes treatment. MATERIALS AND METHODS: Micro ribonucleic acid (miR)-363, NOTCH1 and forkhead box C2 (FOXC2) expressions in high glucose (HG)-treated HepG2 cells and the livers of type 2 diabetes mellitus rats were assessed using quantitative polymerase chain reaction. Protein levels of NOTCH1, FOXC2 and phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein kinase (Akt)-related proteins were evaluated using western blot. Lipid accumulation was determined using Oil Red O staining. Then glucose consumption, blood glucose level and glycogen content were detected using kits. Finally, dual luciferase reporter assay was used to verify the binding relationship between miR-363 and NOTCH1, and the binding relationship between miR-363 and FOXC2. RESULTS: MiR-363 was significantly upregulated in the livers of diabetic rats and HG-induced HepG2 cells, whereas NOTCH1 and FOXC2 were downregulated. In HG-induced HepG2 cells, miR-363 inhibitor markedly increased glucose consumption and uptake, and reduced accumulation of lipid droplets. Then NOTCH1 and FOXC2 were identified as downstream targets of miR-363. NOTCH1 overexpression or FOXC2 overexpression could ameliorate glucose and lipids metabolism disorder in type 2 diabetes model cells. In addition, we found that FOXC2 inhibition abolished the effect of NOTCH1 overexpression on HG-induced HepG2 cells. Finally, we proved that the PI3K/Akt pathway was the downstream pathway of FOXC2. CONCLUSION: MiR-363 was considered as a key regulator of glucose and lipids metabolism in type 2 diabetes mellitus, which regulated PI3K/Akt axis by targeting NOTCH1 and FOXC2, thus leading to hepatic glucose and lipids metabolism disorder in type 2 diabetes.
