Diabetic nephropathy (DN) is a serious complication of diabetes mellitus. Long non-coding RNAs (lncRNAs) are regulators in DN progression. However, the regulatory mechanisms of multiple lncRNAs in DN remain to be determined. Our aim was to investigate the function and molecular mechanism of lncRNA RNA component of mitochondrial RNAase P (Rmrp) in DN. Here, we observed that the expression of Rmrp was up-regulated in the kidney of db/db DN mice and high glucose induced glomerular mesangial cells (MC). More importantly, the abnormal transcription of Rmrp was induced by nuclear transcription factor Sp1, which promotes the proliferation and production of fibrotic markers in MC. Subsequently, we screened the miRNAs related to Rmrp and found that Rmrp and miR-1a-3p are co-localized at the subcellular level of MC, and Rmrp could directly binds to miR-1a-3p. Further mechanism research demonstrated that the elevated miR-1a-3p significantly attenuated the proliferation and fibrosis-promoting effects induced by up-regulation of Rmrp. At the same time, we also investigated that miR-1a-3p can directly bind to Jun D proto-oncogene (JunD), thereby regulating the protein level of JunD. Rmrp-induced proliferation and fibrogenesis were reversed by co-transfection with JunD siRNA. In summary, Sp1 induced lncRNA Rmrp could drive the expression of JunD via sponging miR-1a-3p in DN progression.

中文翻译：

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Sp1 诱导的 lncRNA Rmrp 通过调节 miR-1a-3p/JunD 通路促进糖尿病肾病中的系膜细胞增殖和纤维化。

糖尿病肾病（DN）是糖尿病的严重并发症。长链非编码 RNA (lncRNA) 是 DN 进展的调节剂。然而，DN中多种lncRNA的调控机制仍有待确定。我们的目的是研究 DN 中线粒体 RNA 酶 P (Rmrp) 的 lncRNA RNA 组分的功能和分子机制。在这里，我们观察到 Rmrp 的表达在 db/db DN 小鼠和高糖诱导的肾小球系膜细胞 (MC) 的肾脏中上调。更重要的是，Rmrp 的异常转录是由核转录因子 Sp1 诱导的，它促进了 MC 中纤维化标志物的增殖和产生。随后，我们筛选了与 Rmrp 相关的 miRNA，发现 Rmrp 和 miR-1a-3p 共定位于 MC 的亚细胞水​​平，Rmrp 可以直接与 miR-1a-3p 结合。进一步的机制研究表明，升高的 miR-1a-3p 显着减弱了由 Rmrp 上调诱导的增殖和纤维化促进作用。同时，我们还研究了miR-1a-3p可以直接结合JunD原癌基因（JunD），从而调节JunD的蛋白水平。Rmrp 诱导的增殖和纤维化通过与 JunD siRNA 共转染逆转。总之，Sp1 诱导的 lncRNA Rmrp 可以通过在 DN 进展中海绵 miR-1a-3p 来驱动 JunD 的表达。从而调节 JunD 的蛋白质水平。Rmrp 诱导的增殖和纤维化通过与 JunD siRNA 共转染逆转。总之，Sp1 诱导的 lncRNA Rmrp 可以通过在 DN 进展中海绵 miR-1a-3p 来驱动 JunD 的表达。从而调节 JunD 的蛋白质水平。Rmrp 诱导的增殖和纤维化通过与 JunD siRNA 共转染逆转。总之，Sp1 诱导的 lncRNA Rmrp 可以通过在 DN 进展中海绵 miR-1a-3p 来驱动 JunD 的表达。