Circular E3 ubiquitin-protein ligase improves renal function and alleviates inflammation and renal injury in chronic glomerulonephritis rats via the microRNA-146a-5p / tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma axis.

Abstract

Circular E3 ubiquitin-protein ligase (circ-ITCH), a novel circRNA, is generated from several exons of itchy E3 ubiquitin protein ligase. Reports on circ-ITCH have discussed its pathogenic performance in human diseases. Based on this, this study determines whether and how circ-ITCH is involved in the pathogenesis of chronic glomerulonephritis (CGN). First, a rat model of CGN induced by cationic bovine serum albumin was established. Then, CGN rats were injected with lentiviruses interfering with the expression of circ-ITCH, miR-146a-5p or tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG). Then, blood urea nitrogen and serum creatinine levels were measured to evaluate renal function; inflammatory factor content and fibrosis marker expression in kidney tissue were detected; renal pathological damage was analyzed by hematoxylin-eosin staining and periodic acid-Schiff staining. Finally, the binding relationship between miR-146a-5p and circ-ITCH or YWHAG was verified. Elevating circ-ITCH or depleting miR-146a-5p improved renal function (both P<0.05), reduced inflammatory factor content and fibrosis marker expression (all P<0.05) and alleviated renal pathological damage in CGN rats. Circ-ITCH negatively regulated miR-146a-5p expression by adsorbing miR-146a-5p (P<0.05), and miR-146a-5p inhibited YWHAG expression by binding to the 3'-UTR of YWHAG (P<0.05). Loss of YWHAG reversed the protective effect of upregulated circ-ITCH in CGN rats (all P<0.05). We conclude that circ-ITCH improves renal function and attenuates inflammation and renal injury in rats with CGN via the miR-146a-5p/YWHAG axis.