miR-15a-5p suppresses peritoneal fibrosis induced by peritoneal dialysis via targeting VEGF in rats.

Abstract:

AIM:When peritoneal fibrosis (PF) causes ultrafiltration failure in peritoneal dialysis (PD) patients, PD has to be discontinued. Currently, there is no effective way to relieve PF. In this study, we aimed to determine whether miR-15a-5p is involved in PF and to determine the underlying mechanism. METHODS:Six normal rats were used as the control group. A uremic rat model was constructed using 5/6 nephrectomy in a Sprague-Dawley model. The uremic rats were randomly divided into PD, lentivirus-transfected, negative control, VEGFR-inhibited and gavage control groups. Except for the control group, all uremia rats received continuous PD for 28 days. In the lentivirus-transfected group, the miR-15a-5p plasmid was injected into the peritoneal cavity to upregulate miR-15a-5p expression. Axitinib was used to block vascular endothelial growth factor receptor (VEGFR) in the peritoneum. The mRNA levels of miR-15a-5p and VEGF were detected by qRT-PCR and FISH. Protein levels of VEGF, E-cadherin, collagen IV, fibronectin and α-SMA were detected by western blot and immunohistochemistry. RESULTS:PD leads to peritoneal thickening and fibrosis. The expression level of miR-15a-5p decreased and that of VEGF increased in the PD group than in the controls. Additionally, E-cadherin was significantly reduced while collagen IV, fibronectin and α-SMA were obviously increased in the PD group compared to controls. FISH showed that VEGF might be the target gene of miR-15a-5p. Overexpression of miR-15a-5p or inhibition of VEGFR could reverse PF. CONCLUSION:miR-15a-5p may participate in the endothelial to mesenchymal transition of PF caused by PD through VEGF.

journal_name

Ren Fail

journal_title

Renal failure

authors

He Q,Wen L,Wang L,Zhang Y,Yu W,Zhang F,Zhang W,Xiao J,Wen X,Zhao Z

doi

10.1080/0886022X.2020.1811123

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

932-943

issue

1

eissn

0886-022X

issn

1525-6049

journal_volume

42

pub_type

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