HIF1A and VEGF regulate each other by competing endogenous RNA mechanism and involve in the pathogenesis of peritoneal fibrosis.
Adult
Aged
Cell Line
Dialysis Solutions
/ chemistry
Female
Gene Expression Profiling
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
/ analysis
Kidney Diseases
/ therapy
Male
MicroRNAs
/ genetics
Middle Aged
Peritoneal Dialysis
/ adverse effects
Peritoneal Fibrosis
/ etiology
RNA Interference
Vascular Endothelial Growth Factor A
/ analysis
Competing endogenous RNA
HIF1A
Peritoneal fibrosis
VEGF
microRNA
Journal
Pathology, research and practice
ISSN: 1618-0631
Titre abrégé: Pathol Res Pract
Pays: Germany
ID NLM: 7806109
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
06
10
2018
revised:
05
12
2018
accepted:
24
12
2018
pubmed:
2
1
2019
medline:
14
6
2019
entrez:
2
1
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 30598338
pii: S0344-0338(18)31355-4
doi: 10.1016/j.prp.2018.12.022
pii:
doi:
Substances chimiques
Dialysis Solutions
0
HIF1A protein, human
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
MicroRNAs
0
Vascular Endothelial Growth Factor A
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
644-652Informations de copyright
Copyright © 2018 Elsevier GmbH. All rights reserved.