1. HIF1A and VEGF regulate each other by competing endogenous RNA mechanism and involve in the pathogenesis of peritoneal fibrosis.
- Author
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Li J, Li SX, Gao XH, Zhao LF, Du J, Wang TY, Wang L, Zhang J, Wang HY, Dong R, and Guo ZY
- Subjects
- Adult, Aged, Cell Line, Female, Gene Expression Profiling, Humans, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Male, MicroRNAs genetics, Middle Aged, Peritoneal Fibrosis etiology, Peritoneal Fibrosis pathology, RNA Interference, Vascular Endothelial Growth Factor A genetics, Dialysis Solutions chemistry, Hypoxia-Inducible Factor 1, alpha Subunit analysis, Kidney Diseases therapy, Peritoneal Dialysis adverse effects, Peritoneal Fibrosis metabolism, Vascular Endothelial Growth Factor A analysis
- Abstract
Background: Peritoneal fibrosis is a major intractable complication of long-term peritoneal dialysis, and would eventually lead to peritoneal ultrafiltration failure and the termination of peritoneal dialysis. Hypoxia-inducible factor 1-alpha (HIF1A) has been reported to regulate vascular endothelial growth factor (VEGF) and involves in peritoneal fibrosis, but the exact molecular regulation mechanism remains unknown., Methods: HIF1A and VEGF protein levels were measured in 42 peritoneal patients using enzyme linked immunosorbent assay. Bioinformatics, reverse transcription-polymerase chain reaction, correlation analysis, RNA interference, gene over-expression and luciferase assays were performed to clarify the competing endogenous RNA (ceRNA) regulation between HIF1A and VEGF., Results: Both HIF1A and VEGF levels were elevated in the peritoneal effluent of peritoneal dialysis patients with ultrafiltration problems, and were positively correlated with each other at protein level and mRNA level. Bioinformatics analysis identified 8 common targeted miRNAs for HIF1A and VEGF, including miR-17-5p, 20a, 20b, 93, 106a, 106b, 199a-5p and 203. MiR-17-5p was proved to be present in patients' peritoneal effluent and selected for further studies. HIF1A mRNA and VEGF mRNA could regulate each other, and miR-17-5p was required in the regulations. Down/up regulation of HIF1A mRNA and VEGF mRNA resulted in up/down regulation of miR-17-5p. Furthermore, down/up regulation of miR-17-5p was associated with up/down regulation of HIF1A mRNA and VEGF mRNA. Luciferase assay indicated that HIF1A and VEGF regulated each other through 3'UTR., Conclusion: HIF1A and VEGF could regulate each other in peritoneal mesothelial cell in the mediation of miR-17-5p and 3'UTR, indicating HIF1A and VEGF might regulate each other through competing endogenous RNA mechanism in the development of peritoneal fibrosis., (Copyright © 2018 Elsevier GmbH. All rights reserved.)
- Published
- 2019
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