Silenced miR-21 inhibits renal interstitial fibrosis via targeting ERK1/2 signaling pathway in mice.

Abstract

To study the influence of micro ribonucleic acid (miR)-21 on the renal interstitial fibrosis (RIF) model mice, and to preliminarily elucidate the mechanism of action of miR-21 in the development of RIF by studying the influences of miR-21 on the expressions of the proteins related to the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway and its downstream proteins. The mouse model of the left unilateral ureteral obstruction (UUO) was established. The experimental mice were divided into the Sham group and UUO group and were normally fed for 3 weeks. Then, they were executed, and their blood was extracted to determine the renal function-related indicators. The left kidney was excised, and the corresponding specimens were reserved for observing the appearance of the kidney and the morphology of the renal tubules and interstitium. The relative expression levels of epithelial (E-)cadherin, α-smooth muscle actin (α-SMA), and ERK1/2 phosphorylated ERK1/2 (p-ERK1/2), the transforming growth factor-β1 (TGF-β1) and the connective tissue growth factor (CTGF) proteins in renal tissues were determined. After the human renal proximal tubular epithelial cell line, the human kidney-2 (HK-2) was treated with high glucose (HG) combined with silenced miR-21 or the ERK1/2 inhibitor PD98059, the relative expression levels of ɑ-SMA and TGF-β1 protein were measured. UUO group had significantly higher content of blood urea nitrogen (BUN), serum creatinine (SCr), and uric acid (UA) than the Sham group, and exhibited the infiltration of renal interstitial monocytes and lymphocytes, renal tubular podocyte damage, phenotypic transformation and atrophy, the activation and proliferation of interstitial fibroblasts, and excessive deposition of extracellular matrix (ECM). Moreover, the expression level of E-cadherin in the renal tissues was decreased, but the relative expression levels of ɑ-SMA, and TGF-β1, CTGF, and p-ERK1/2 proteins were evidently elevated. Lower relative expression levels of ɑ-SMA and TGF-β1 protein were detected in the human renal proximal tubular epithelial cell line HK-2 after the combined treatment with HG and silenced miR-21 or the ERK1/2 inhibitor PD98059. MiR-21 may be related to the occurrence and development of RIF. Silenced miR-21 probably suppresses RIF via the ERK1/2 signaling pathway.