Metformin Regulating miR-34a Pathway to Inhibit Egr1 in Rat Mesangial Cells Cultured with High Glucose.

ABSTRACT: Background:Activating AMPK? negatively regulates Egr1 to inhibit inflammatory cytokines in high glucose. miR-34a inhibition increases phosphorylated AMPK? through mediating SIRT1 to suppress the development of fatty liver. Aim of the Study:To clarify the function of Egr1 on the inflammation and fibrosis in high glucose-cultured MCs, as well as to explore the effects of metformin on miR-34a pathway and Egr1 expression. Methods:We transfected MCs with miR-34a inhibitor. And MCs were transfected with small interfering RNA for silencing Egr1 and SIRT1. Quantitative real-time PCR was used to assay the transcription levels of Egr1 mRNA and miR-34a. Western blot was used to test the protein. And ELISA was used to measure inflammatory factors. Results:High glucose upregulates Egr1 to aggravate the inflammation and fibrosis in MCs. miR-34a suppresses the activation of SIRT1/AMPK? and results in promoting Egr1 in high glucose-cultured MCs. Metformin attenuates high glucose-stimulated inflammation and fibrosis in MCs by regulating miR-34a-mediated SIRT1/AMPK? activity and the downstream Egr1 protein. Conclusion:We enriched the effects of miR-34a pathway regulating Egr1 in high glucose-cultured MCs. It provides a foundation for future researches considering Egr1 as a therapeutic target and a new direction for the clinical application of metformin in early DKD.

SUBMITTER: Wu C 

PROVIDER: S-EPMC5841108 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature