Background: Activating AMPKα negatively regulates Egr1 to inhibit inflammatory cytokines in high glucose. miR-34a inhibition increases phosphorylated AMPKα 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/AMPKα 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/AMPKα 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.