Long non-coding RNA Rpph1 promotes inflammation and proliferation of mesangial cells in diabetic nephropathy via an interaction with Gal-3
Long non-coding RNA Rpph1 promotes inflammation and proliferation of mesangial cells in diabetic nephropathy via an interaction with Gal-3
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长链非编码RNA Rpph1通过与Gal-3相互作用促进糖尿病肾病肾小球系膜细胞炎症和增殖
DOI：
10.1038/s41419-019-1765-0
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发表时间：
2019-07-08
影响因子：
9
通讯作者：
Zhang, Zheng
中科院分区：
文献类型：
--
作者：
Zhang, Panyang;Sun, Yan;Zhang, Zheng
糖尿病肾病（DN）是糖尿病最重要的并发症之一，是终末期肾病的主要原因。越来越多的证据表明，肾脏炎症在DN的发生和发展中起作用，但确切的细胞机制尚不清楚。长链非编码RNA（lncRNA）的不规则表达存在于包括DN在内的许多疾病中。然而，lncRNA与DN炎症的关系尚不清楚。在这项研究中，我们确定了差异表达的lncRNA在DN使用RNA测序。在这些lncRNA中，我们使用定量实时PCR在体内和体外鉴定了七种DN相关lncRNA。特别是一种lncRNA，Rpph 1（核糖核酸酶P RNA组分H1），表现出显着增加的表达。此外，Rpph 1的过表达或敲低被发现可以调节系膜细胞（MCs）中的细胞增殖和炎症细胞因子的表达。结果表明，Rpph 1直接与DN相关因子半乳糖凝集素-3（Gal-3）相互作用。此外，Rpph 1的过表达通过Gal-3/Mek/Erk信号通路促进低葡萄糖条件下MC中的炎症和细胞增殖，而Rpph 1的敲低通过Gal-3/Mek/Erk通路抑制高糖条件下MC中的炎症和细胞增殖。这些结果提供了新的见解之间的关联Rpph 1和Gal-3/Mek/Erk信号通路在DN的进展。
Diabetic nephropathy (DN) is one of the most significant complications of diabetes and is the primary cause of end-stage kidney disease. Cumulating evidence has shown that renal inflammation plays a role in the development and progression of DN, but the exact cellular mechanisms are unclear. Irregular expression of long non-coding RNAs (lncRNAs) is present in many diseases, including DN. However, the relationship between lncRNAs and inflammation in DN is unclear. In this study, we identified differentially expressed lncRNAs in DN using RNA-sequencing. Among these lncRNAs, we identified seven DN-related lncRNAs in vivo and in vitro using quantitative real-time PCR. One lncRNA in particular, Rpph1 (ribonuclease P RNA component H1), exhibited significantly increased expression. Further, over-expression or knockdown of Rpph1 was found to regulate cell proliferation and the expression of inflammatory cytokines in mesangial cells (MCs). The results revealed that Rpph1 directly interacts with the DN-related factor galectin-3 (Gal-3). Further, over-expression of Rpph1 promoted inflammation and cell proliferation through the Gal-3/Mek/Erk signaling pathway in MCs under low glucose conditions, while knockdown of Rpph1 inhibited inflammation and cell proliferation through the Gal-3/Mek/Erk pathway in MCs under high glucose conditions. These results provide new insight into the association between Rpph1 and the Gal-3/Mek/Erk signaling pathway during DN progression.