Department of Pathophysiology, Guizhou Medical University, Guiyang, 550025, China.
Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research On Common Chronic Diseases, Guizhou Medical University, Guiyang, 550025, China.
Hum Cell. 2023 May;36(3):1024-1040. doi: 10.1007/s13577-023-00877-8. Epub 2023 Feb 24.
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 (Ca) 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.
肾间质纤维化（RIF）是进行性慢性肾脏病（CKD）的常见病理标志。环状 RNA（circRNA）参与某些肾脏疾病，但它们在 RIF 中的作用在很大程度上尚不清楚。本研究探讨了 circRNA_0017076 在 RIF 中的作用及其潜在机制。在转化生长因子-β1（TGF-β1）处理的肾小管上皮细胞（RTEC）和 RIF 患者肾活检样本中，circRNA_0017076 的表达明显上调。功能测定表明，circRNA_0017076 与 microRNA-185-5p（miR-185-5p）共定位，并通过与 miR-185-5p 的直接结合抑制 miR-185-5p 的功能。在体外，circRNA_0017076 的敲低抑制了 RTEC 中钙离子（Ca）流入介导的上皮-间充质转化（EMT），并下调了基质相互作用分子 1（STIM1）的表达，STIM1 是 miR-185-5p 的靶蛋白。沉默 mmu_circ_0004488 通过靶向 miR-185-5p/Stim1 轴减少单侧输尿管梗阻（UUO）小鼠肾脏中的纤维化病变。我们首次鉴定 circRNA_0017076 为 miR-185-5p 的海绵，调节 STIM1 基因表达并参与 RIF。我们的研究结果支持 circRNA_0017076 作为 RIF 疾病的潜在治疗靶点。
