Down-regulation of GRα expression and inhibition of its nuclear translocation by hypoxia

Life Sciences
Pei ZhangRong-Yu Liu

Abstract

Glucocorticoids are the most effective anti-inflammatory agent in treating pulmonary diseases typically accompanied by hypoxia. Our previous study has demonstrated that glucocorticoid receptor α (GRα) expression is reduced in hypoxia but the underlying mechanism remains elusive. In this study we aim to identify the signaling pathway involved in hypoxia-induced down-regulation of GRα, and whether hypoxia affects nuclear translocation of GRα. Female C57BL/6 mice were sensitized with saline or ovalbumin (OVA) as the in vivo model. Mice were divided into control and OVA groups, and their lung histology and the expression of hypoxia inducible factor (HIF-1) and GRα were examined. A549 cells were exposed to chemical hypoxia as the in vitro model, where mitogen-activated protein kinases (MAPKs) were inhibited specifically by SB203580. Next, under normal or hypoxic conditions, the expression of GRα, MAPKs and HIF-1 signal protein were determined by Western blot analysis, and GRα translocation were observed through live-cell imaging. In OVA challenged mice the expression of GRα was down-regulated whereas HIF-1 was up-regulated. Hypoxia caused a time-dependent decrease of GRα expression, and activated multiple signaling pathways includin...Continue Reading

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Citations

Apr 24, 2019·Journal of Assisted Reproduction and Genetics·Daniela Antunes MontaniEdson Guimarães Lo Turco
Jun 7, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Xiufeng TangRenhui Liu
Oct 3, 2019·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·P Naomi FrancoWilliam J Pearce

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