Department of Rheumatology, The First Affiliated Hospital of Zhengzhou University, 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China.
Arthritis Res Ther. 2021 Jan 13;23(1):24. doi: 10.1186/s13075-020-02404-8.
Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Circular RNAs (circRNAs) can act as competitive endogenous RNAs (ceRNAs) to regulate gene transcription, which is involved in mechanism of many diseases. However, the role of circRNA in lupus nephritis has been rarely reported. In this study, we aim to investigate the clinical value of circRNAs and explore the mechanism of circRNA involvement in the pathogenesis of LN.
Renal tissues from three untreated LN patients and three normal controls (NCs) were used to identify differently expressed circRNAs by next-generation sequencing (NGS). Validated assays were used by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The interactions between circRNA and miRNA, or miRNA and mRNA were further determined by luciferase reporter assay. The extent of renal fibrosis between the two groups was assessed by Masson-trichome staining and immunohistochemistry (IHC) staining.
159 circRNAs were significantly dysregulated in LN patients compared with NCs. The expression of hsa_circ_0123190 was significantly decreased in the renal tissues of patients with LN (P = 0.014). Bio-informatics analysis and luciferase reporter assay illustrated that hsa_circ_0123190 can act as a sponge for hsa-miR-483-3p, which was also validated to interact with APLNR. APLNR mRNA expression was related with chronicity index (CI) of LN (P = 0.033, R = 0.452). Moreover, the fibrotic-related protein, transforming growth factor-β1 (TGF-β1), which was regulated by APLNR, was more pronounced in the LN group (P = 0.018).
Hsa_circ_0123190 may function as a ceRNA to regulate APLNR expression by sponging hsa-miR-483-3p in LN.
狼疮肾炎 (LN) 是系统性红斑狼疮 (SLE) 最严重的并发症之一。环状 RNA (circRNA) 可以作为竞争性内源性 RNA (ceRNA) 调节基因转录，这涉及许多疾病的发病机制。然而，circRNA 在狼疮肾炎中的作用鲜有报道。在本研究中，我们旨在探讨 circRNA 的临床价值，并探索 circRNA 参与 LN 发病机制的机制。
采用下一代测序 (NGS) 技术对 3 例未经治疗的 LN 患者和 3 例正常对照 (NC) 的肾组织进行差异表达 circRNA 鉴定。采用实时定量逆转录聚合酶链反应 (qRT-PCR) 进行验证检测。通过荧光素酶报告基因检测进一步确定 circRNA 与 miRNA 或 miRNA 与 mRNA 之间的相互作用。通过 Masson 三色染色和免疫组织化学 (IHC) 染色评估两组间肾纤维化程度。
与 NC 相比，LN 患者的 159 个 circRNA 表达显著失调。ln 患者肾组织中 hsa_circ_0123190 的表达明显降低 (P = 0.014)。生物信息学分析和荧光素酶报告基因检测表明，hsa_circ_0123190 可作为 hsa-miR-483-3p 的海绵，这也被证实与 APLNR 相互作用。APLNR mRNA 表达与 LN 的慢性指数 (CI) 相关 (P = 0.033, R = 0.452)。此外，由 APLNR 调节的纤维化相关蛋白转化生长因子-β1 (TGF-β1) 在 LN 组更为明显 (P = 0.018)。
hsa_circ_0123190 可能通过海绵吸附 hsa-miR-483-3p 作为 ceRNA 调节 LN 中的 APLNR 表达。
