The Long Noncoding RNA 150Rik Promotes Mesangial Cell Proliferation via miR-451/IGF1R/p38 MAPK Signaling in Diabetic Nephropathy.
BACKGROUND/AIMS
Diabetic nephropathy (DN) as the primary cause of end-stage kidney disease is a common complication of diabetes. However, the initiating molecular events triggering DN are unknown. Recently, long noncoding RNAs (lncRNAs) have been shown to play important roles in DN.


METHODS
The expression level of lncRNA 1500026H17Rik (150Rik for short) was measured by qRT-PCR (quantitative real-time PCR). Cell proliferation ability was detected by 5-Ethynyl-2'-deoxyuridine (EdU). The relationship between 150Rik and microRNA 451 (miR-451) was examined by luciferase assay and RNA immunoprecipitation (RIP) assay. Finally, the effect of 150Rik on cell proliferation through the miR-451/insulin-like growth factor 1 receptor (IGF1R)/mitogen-activated protein kinases (p38MAPK) pathway was detected by EdU, flow cytometry analysis, western blot.


RESULTS
We found that 150Rik, an evolutionarily conserved lncRNA, was significantly upregulated in renal tissue of db/db DN mice and in mesangial cells (MCs) cultured under a high glucose condition. Further, overexpression or knockdown of 150Rik was found to regulate cell proliferation in MCs. Moreover, 150Rik was found to interact with miR-451 in both a direct and argonaute-2 (Ago2)-dependent manner. Results also revealed that overexpression of 150Rik inhibited cell proliferation through the miR-451/IGF1R/p38MAPK pathway in MCs under the high glucose condition, while knockdown of 150Rik increased cell proliferation via the miR-451/IGF1R/p38MAPK pathway.


CONCLUSION
Taken together, these results provide new insight into the association between 150Rik and the miR-451/IGF1R/p38MAPK signaling pathway during DN progression.
['Zhang|Yajuan|Y|', 'Sun|Yan|Y|', 'Peng|Rui|R|', 'Liu|Handeng|H|', 'He|Weihao|W|', 'Zhang|Luyu|L|', 'Peng|Huimin|H|', 'Zhang|Zheng|Z|']
D000818:Animals D049109:Cell Proliferation D003928:Diabetic Nephropathies D008297:Male D050527:Mesangial Cells D008810:Mice, Inbred C57BL D035683:MicroRNAs D062085:RNA, Long Noncoding D017526:Receptor, IGF Type 1 D015398:Signal Transduction D048051:p38 Mitogen-Activated Protein Kinases
Cell proliferation miR-451 Diabetic nephropathy lncRNA