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

Figure 11

Schematic representation of miR-34a regulating SIRT1/AMPKα signaling pathways and Egr1 involved in the HG-induced fibrosis and inflammation in RMCs. High glucose upregulates miR-34a and Egr1 expression, as well as decreases SIRT1 protein and AMPKα phosphorylation expression. miR-34a suppresses the activation of SIRT1/AMPKα and results in promoting Egr1-mediated inflammation and fibrosis in high glucose-cultured RMCs. AICAR activating AMPKα prevents Egr1 expression in high glucose. Meanwhile, metformin attenuates high glucose-stimulated inflammation and fibrosis in RMCs by regulating miR-34a-mediated SIRT1/AMPKα activity and the downstream Egr1 protein. HG: high glucose; SIRT1: sirtuin 1; AMPKα: adenosine monophosphate-activated protein kinase α; AICAR: 5-amino-4-imidazolecarboxamide riboside-1-b-D-ribofuranoside; Egr1: early growth response factor 1; FN: fibronectin; CTGF: connective tissue growth factor; MCP-1: monocyte chemoattractant protein 1; CXCL5: chemokine C-X-C motif ligand 5; RMCs: rat mesangial cells.