Hypoxia-induced hyperpermeability of rat glomerular endothelial cells involves HIF-2α mediated changes in the expression of occludin and ZO-1

This study aimed to investigate the role of hypoxia-inducible factor-2α (HIF-2α) in the expression of tight junction proteins and permeability alterations in rat glomerular endothelial cells (rGENCs) under hypoxia conditions. The expression level of HIF-2α and tight junction proteins (occludin and ZO-1) in rGENCs were examined following 5% oxygen density exposure at different treatment times. HIF-2α lentivirus transfection was used to knockdown HIF-2α expression. Cells were divided into four groups: 1) control group (rGENCs were cultured under normal oxygen conditions), 2) hypoxia group (rGENCs were cultured under hypoxic conditions), 3) negative control group (rGENCs were infected with HIF-2α lentivirus negative control vectors and cultured under hypoxic conditions), and 4) Len group (rGENCs were transfected with HIF-2α lentivirus and cultured under hypoxic conditions). The hypoxia, negative control, and Len groups were kept in a hypoxic chamber (5% O2, 5% CO2, and 90% N2) for 24 h and the total content of occludin and ZO-1, and the permeability of rGENCs were assessed. With increasing hypoxia time, the expression of HIF-2α gradually increased, while the expression of occludin decreased, with a significant difference between groups. ZO-1 expression gradually decreased under hypoxia conditions, but the difference between the 24 and 48 h groups was not significant. The permeability of cells increased following 24-h exposure to hypoxia compared to the control group (P<0.01). The knockdown of HIF-2α expression significantly increased occludin and ZO-1 content compared with hypoxia and negative control groups (P<0.01), while permeability was reduced (P<0.01). Hypoxia increased HIF-2α content, inducing permeability of rGENCs through the reduced expression of occludin and ZO-1.

Bibliographic Details

Main Authors:	Luo,Peng-Li, Wang,Yan-Jun, Yang,Yan-Yan, Yang,Jia-Jia
Format:	Digital revista
Language:	English
Published:	Associação Brasileira de Divulgação Científica 2018
Online Access:	http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2018000700604
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