Abstract
Renal interstitial fibrosis (RIF) is a common pathological hallmark of progressive chronic kidney disease (CKD). Circular RNAs (circRNAs) are involved in certain renal diseases, but their role in RIF is largely unknown. The present study investigated the effects and potential mechanisms of circRNA_0017076 in RIF. CircRNA_0017076 expression was markedly upregulated in transforming growth factor-β1 (TGF-β1)-treated renal tubular epithelial cells (RTECs) and kidney biopsy samples from patients with RIF. Functional assays showed that circRNA_0017076 colocalized with microRNA-185-5p (miR-185-5p) and inhibited miR-185-5p function via direct binding to miR-185-5p. In vitro, the knockdown of circRNA_0017076 inhibited the calcium ion (Ca2+) influx-mediated epithelial-to-mesenchymal transition (EMT) of RTECs and downregulated the expression of stromal interaction molecule 1 (STIM1), which is a target protein of miR-185-5p. Silencing mmu_circ_0004488 reduced fibrotic lesions in the kidneys of unilateral ureteral obstruction (UUO) mice by targeting the miR-185-5p/Stim1 axis. For the first time, we identified circRNA_0017076 as a sponge for miR-185-5p, which regulates STIM1 gene expression and is involved in RIF. Our results support circRNA_0017076 as a potential therapeutic target for RIF disease.