Department of Pathology; Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University; Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, 050017, China.
Department of Rheumatology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, China.
Lab Invest. 2022 Sep;102(9):966-978. doi: 10.1038/s41374-022-00788-6. Epub 2022 May 6.
Circular RNAs (circRNAs) are regulators of gene expression that can regulate cell proliferation and programmed cell death and serve as biomarkers in renal diseases. However, the specific traits and underlying mechanisms of circRNAs in the progression of lupus nephritis (LN) have not been elucidated. In the present study, we clarified that hsa_circ_0054595 (circRTN4) was upregulated in human renal mesangial cells (HRMCs). In cultured HRMCs, circRTN4 could enhance FN expression by directly interacting with miR-513a-5p. High circRTN4 expression in monocytes disseminated into HRMCs in an exosomal manner, thereby accelerating cell proliferation and extracellular matrix deposition. In addition, knockdown of circRTN4 in the kidney or peripheral blood alleviated renal damage in MRL/lpr and BALB/c mice. Clinically, high levels of circRTN4 were found in peripheral blood mononuclear cells and kidney tissues of LN patients, hence serving as an effective biomarker for LN detection and a novel therapeutic target. Our findings indicated that circRTN4 exacerbates mesangial cell dysfunction by activating the miR-513a-5p/FN axis in lupus nephritis.
环状 RNA（circRNAs）是基因表达的调控因子，可调节细胞增殖和程序性细胞死亡，并作为肾脏疾病的生物标志物。然而，circRNAs 在狼疮肾炎（LN）进展中的具体特征和潜在机制尚不清楚。在本研究中，我们阐明 hsa_circ_0054595（circRTN4）在人肾小球系膜细胞（HRMCs）中上调。在培养的 HRMCs 中，circRTN4 可以通过直接与 miR-513a-5p 相互作用来增强 FN 的表达。高表达的 circRTN4 以细胞外小泡的形式扩散到 HRMCs 中，从而加速细胞增殖和细胞外基质沉积。此外，在 MRL/lpr 和 BALB/c 小鼠中敲低肾脏或外周血中的 circRTN4 可减轻肾脏损伤。临床上，LN 患者外周血单个核细胞和肾脏组织中发现高水平的 circRTN4，因此可作为 LN 检测的有效生物标志物和新的治疗靶点。我们的研究结果表明，circRTN4 通过激活 miR-513a-5p/FN 轴在狼疮肾炎中加重系膜细胞功能障碍。
