MiR-21 promotes calcium oxalate-induced renal tubular cell injury by targeting PPARA.

MiR-21 promotes calcium oxalate-induced renal tubular cell injury by targeting PPARA. Am J Physiol Renal Physiol. 2020 Jul 06;: Authors: Su B, Han H, Ji C, Hu W, Yao J, Yang J, Fan Y, Li J Abstract Kidney stone disease is a crystal concretion formed in kidneys which has been associated with an increased risk of chronic kidney disease. MicroRNAs are functionally involved in kidney injury. Data mining using a microRNA array database suggested that miR-21 may be associated with calcium oxalate monohydrate (COM)-induced renal tubular cell injury. Here, we confirmed that COM exposure significantly upregulated miR-21 expression, inhibited proliferation, promoted apoptosis and caused lipid accumulation in the immortalized renal tubular cell line HK-2. Moreover, inhibition of miR-21 enhanced proliferation and decreased apoptosis and lipid accumulation in HK-2 cells upon COM exposure. In a glyoxylate-induced mouse model of renal calcium oxalate deposition, increased miR-21 expression, lipid accumulation and kidney injury were also observed. In silico analysis and subsequent experimental validation confirmed PPARA, a key gene in fatty acid oxidation, as a direct miR-21 target. Suppression of miR-21 by miRNA antagomiR or activation of PPARĪ± by its selective agonist fenofibrate significantly reduced renal lipid accumulation and protected against renal injury in vivo. In addition, miR-21 was significantly increased in urine samples from patients...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research