Department of Nephrology, Xiangyang No.1 People's Hospital Affiliated of Hubei University of Medicine, Xiangyang, China.
Department of Nephrology, Xiangyang No.1 People's Hospital Affiliated of Hubei University of Medicine, Xiangyang, China.
Gene. 2020 Nov 30;761:144971. doi: 10.1016/j.gene.2020.144971. Epub 2020 Jul 22.
Diabetic nephropathy (DN) is a serious microvascular complication of diabetes across the world. Recently, many circular RNAs (circRNAs) can exert a crucial role in DN progression. Our investigation was designed to study whether circ_0123996 was associated with DN and aimed to find out the underlying mechanisms. We observed that circ_0123996 expression was significantly increased in Type 2 diabetes (T2D) with DN in comparison to those patients without DN. Consistently, circ_0123996 was also obviously elevated in DN mice models and high glucose (HG)-incubated MMCs. Then, it was proved transfection of circ_0123996 siRNA in mice mesangial cells (MMCs) restrained MMCs proliferation greatly. In addition, it was demonstrated that decrease of circ_0123996 alleviated fibrosis-related protein expression including FN and Col-4 in MMCs. Next, it was confirmed by our study that circ_0123996 can serve as a sponge for miR-149-5p. miR-149-5p has been identified in several diseases including diabetes. At present, we observed that miR-149-5p was decreased in DN. Overexpression of miR-149-5p greatly repressed the effect of circ_0123996 on MMCs. BTB and CNC homology 1 (Bach1) is reported in various disease including some vascular diseases.Here, Bach1 was confirmed as a target of miR-149-5p. Circ_0123996 upregulated Bach1 expression and restrained MMCs proliferation and fibrosis through sponging miR-149-5p. Thus, it was revealed that circ_0123996 was involved in DN via sponging miR-149-5p and modulating Bach1 expression.
糖尿病肾病（DN）是全球范围内糖尿病的一种严重的微血管并发症。最近，许多环状 RNA（circRNA）在 DN 进展中发挥着关键作用。我们的研究旨在探讨 circ_0123996 是否与 DN 相关，并试图找出其潜在机制。我们观察到，与无 DN 的 T2D 患者相比，DN 患者的 circ_0123996 表达显著增加。同样，DN 小鼠模型和高糖（HG）孵育的肾小球系膜细胞（MMCs）中 circ_0123996 的表达也明显升高。然后，证明在小鼠系膜细胞（MMCs）中转染 circ_0123996 siRNA 可显著抑制 MMCs 的增殖。此外，还证明 circ_0123996 的下调可减轻 MMCs 中纤维相关蛋白（包括 FN 和 Col-4）的表达。接下来，我们的研究证实 circ_0123996 可作为 miR-149-5p 的海绵。miR-149-5p 已在包括糖尿病在内的几种疾病中得到鉴定。目前，我们观察到 miR-149-5p 在 DN 中减少。miR-149-5p 的过表达可显著抑制 circ_0123996 对 MMCs 的作用。BTB 和 CNC 同源结构域 1（Bach1）已在包括某些血管疾病在内的多种疾病中得到报道。在这里，Bach1 被证实是 miR-149-5p 的靶标。Circ_0123996 通过海绵吸附 miR-149-5p 上调 Bach1 表达，并抑制 MMCs 的增殖和纤维化。因此，研究揭示了 circ_0123996 通过海绵吸附 miR-149-5p 并调节 Bach1 表达参与 DN 的发生发展。
