Abstract
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.
Highlights
Diabetic nephropathy (DN) is one of the main causes of end-stage renal disease[1]
To understand the relationship between long non-coding RNAs (lncRNAs) and DN, we examined the lncRNAs in the renal tissue of db/db DN mice and in normal controls using RNA-seq
The data revealed that 2766 lncRNAs were detected and 95 lncRNAs were dysexpressed in DN, 46 of these were upregulated and 49 were down-regulated (Fig. 1a and Supplementary Table 1)
Summary
Diabetic nephropathy (DN) is one of the main causes of end-stage renal disease[1]. Recent studies suggest that renal inflammation is essential for promoting DN development[5,6]. Many scholars have found that inflammation can lead to kidney damage in the development of DN7–9. LncRNAs can directly interact with several RNA molecules or proteins to regulate the expression of target genes at the transcriptional and post-transcriptional level[13,14,15]. They play a key role in many life processes, such as epigenetic regulation, cell cycle regulation, and differentiation regulation[16,17]
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