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...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.1155/2019/3013765 |
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| author | Xin Xi Jing Zhang Jian Wang Yuqin Chen Wenmei Zhang Xiaoping Zhang Jie Du Guangfa Zhu |
| author_facet | Xin Xi Jing Zhang Jian Wang Yuqin Chen Wenmei Zhang Xiaoping Zhang Jie Du Guangfa Zhu |
| author_sort | Xin Xi |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-e7a4de268e4b406599596a59307248c1 |
| institution | OA Journals |
| issn | 2210-7177 2210-7185 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-e7a4de268e4b406599596a59307248c12025-08-20T02:21:10ZengWileyAnalytical Cellular Pathology2210-71772210-71852019-01-01201910.1155/2019/30137653013765SGK1 Mediates Hypoxic Pulmonary Hypertension through Promoting Macrophage Infiltration and ActivationXin Xi0Jing Zhang1Jian Wang2Yuqin Chen3Wenmei Zhang4Xiaoping Zhang5Jie Du6Guangfa Zhu7Department of Pulmonary and Critical Care, Beijing Anzhen Hospital, Capital Medical University, Beijing, ChinaBeijing Institute of Heart, Lung and Blood Vessel Diseases, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Collaborative Innovation Center for Cardiovascular Disorders, Beijing, ChinaState Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The 1st Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The 1st Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Pulmonary and Critical Care, Beijing Anzhen Hospital, Capital Medical University, Beijing, ChinaBeijing Institute of Heart, Lung and Blood Vessel Diseases, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Collaborative Innovation Center for Cardiovascular Disorders, Beijing, ChinaBeijing Institute of Heart, Lung and Blood Vessel Diseases, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Collaborative Innovation Center for Cardiovascular Disorders, Beijing, ChinaDepartment of Pulmonary and Critical Care, Beijing Anzhen Hospital, Capital Medical University, Beijing, ChinaInflammation 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.http://dx.doi.org/10.1155/2019/3013765 |
| spellingShingle | Xin Xi Jing Zhang Jian Wang Yuqin Chen Wenmei Zhang Xiaoping Zhang Jie Du Guangfa Zhu SGK1 Mediates Hypoxic Pulmonary Hypertension through Promoting Macrophage Infiltration and Activation Analytical Cellular Pathology |
| 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 |
| url | http://dx.doi.org/10.1155/2019/3013765 |
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