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SGK1 Mediates Hypoxic Pulmonary Hypertension through Promoting Macrophage Infiltration and Activation
Inflammation plays a pivotal role in the development of pulmonary arterial hypertension (PAH). Meanwhile, serum glucocorticoid-regulated kinase-1 (SGK1) has been considered to be an important factor in the regulation of inflammation in some vascular disease. However, the role of SGK1 in hypoxia-indu...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877960/ https://www.ncbi.nlm.nih.gov/pubmed/31815093 http://dx.doi.org/10.1155/2019/3013765 |
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author | Xi, Xin Zhang, Jing Wang, Jian Chen, Yuqin Zhang, Wenmei Zhang, Xiaoping Du, Jie Zhu, Guangfa |
author_facet | Xi, Xin Zhang, Jing Wang, Jian Chen, Yuqin Zhang, Wenmei Zhang, Xiaoping Du, Jie Zhu, Guangfa |
author_sort | Xi, Xin |
collection | PubMed |
description | Inflammation plays a pivotal role in the development of pulmonary arterial hypertension (PAH). Meanwhile, serum glucocorticoid-regulated kinase-1 (SGK1) has been considered to be an important factor in the regulation of inflammation in some vascular disease. However, the role of SGK1 in hypoxia-induced inflammation and PAH is still unknown. WT and SGK1(−/−) mice were exposed to chronic hypoxia to induce PAH. The quantitative PCR and immunohistochemistry were used to determine the expression of SGK1. The right ventricular hypertrophy index (RVHI), RV/BW ratio, right ventricle systolic pressure (RVSP), and percentage of muscularised vessels and medical wall thickness were measured to evaluate PAH development. The infiltration of macrophages and localization of SGK1 on cells were examined by histological analysis. The effects of SGK1 on macrophage function and cytokine expression were assessed by comparing WT and SGK1(−/−) macrophages in vitro. SGK1 has high expression in hypoxia-induced PAH. Deficiency of SGK1 prevented the development of hypoxia-induced PAH and inhibited macrophage infiltration in the lung. In addition, SGK1 knockout inhibited the expression of proinflammatory cytokines in macrophages. SGK1-induced macrophage activation and proinflammatory response contributes to the development of PAH in hypoxia-treated mice. Thus, SGK1 might be considered a promising target for PAH treatment. |
format | Online Article Text |
id | pubmed-6877960 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-68779602019-12-08 SGK1 Mediates Hypoxic Pulmonary Hypertension through Promoting Macrophage Infiltration and Activation Xi, Xin Zhang, Jing Wang, Jian Chen, Yuqin Zhang, Wenmei Zhang, Xiaoping Du, Jie Zhu, Guangfa Anal Cell Pathol (Amst) Research Article Inflammation plays a pivotal role in the development of pulmonary arterial hypertension (PAH). Meanwhile, serum glucocorticoid-regulated kinase-1 (SGK1) has been considered to be an important factor in the regulation of inflammation in some vascular disease. However, the role of SGK1 in hypoxia-induced inflammation and PAH is still unknown. WT and SGK1(−/−) mice were exposed to chronic hypoxia to induce PAH. The quantitative PCR and immunohistochemistry were used to determine the expression of SGK1. The right ventricular hypertrophy index (RVHI), RV/BW ratio, right ventricle systolic pressure (RVSP), and percentage of muscularised vessels and medical wall thickness were measured to evaluate PAH development. The infiltration of macrophages and localization of SGK1 on cells were examined by histological analysis. The effects of SGK1 on macrophage function and cytokine expression were assessed by comparing WT and SGK1(−/−) macrophages in vitro. SGK1 has high expression in hypoxia-induced PAH. Deficiency of SGK1 prevented the development of hypoxia-induced PAH and inhibited macrophage infiltration in the lung. In addition, SGK1 knockout inhibited the expression of proinflammatory cytokines in macrophages. SGK1-induced macrophage activation and proinflammatory response contributes to the development of PAH in hypoxia-treated mice. Thus, SGK1 might be considered a promising target for PAH treatment. Hindawi 2019-11-13 /pmc/articles/PMC6877960/ /pubmed/31815093 http://dx.doi.org/10.1155/2019/3013765 Text en Copyright © 2019 Xin Xi et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Xi, Xin Zhang, Jing Wang, Jian Chen, Yuqin Zhang, Wenmei Zhang, Xiaoping Du, Jie Zhu, Guangfa SGK1 Mediates Hypoxic Pulmonary Hypertension through Promoting Macrophage Infiltration and Activation |
title | SGK1 Mediates Hypoxic Pulmonary Hypertension through Promoting Macrophage Infiltration and Activation |
title_full | SGK1 Mediates Hypoxic Pulmonary Hypertension through Promoting Macrophage Infiltration and Activation |
title_fullStr | SGK1 Mediates Hypoxic Pulmonary Hypertension through Promoting Macrophage Infiltration and Activation |
title_full_unstemmed | SGK1 Mediates Hypoxic Pulmonary Hypertension through Promoting Macrophage Infiltration and Activation |
title_short | SGK1 Mediates Hypoxic Pulmonary Hypertension through Promoting Macrophage Infiltration and Activation |
title_sort | sgk1 mediates hypoxic pulmonary hypertension through promoting macrophage infiltration and activation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877960/ https://www.ncbi.nlm.nih.gov/pubmed/31815093 http://dx.doi.org/10.1155/2019/3013765 |
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