NDLI: Serum–Glucocorticoid Regulated Kinase 1 Regulates Macrophage Recruitment and Activation Contributing to Monocrotaline-Induced Pulmonary Arterial Hypertension

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Serum–Glucocorticoid Regulated Kinase 1 Regulates Macrophage Recruitment and Activation Contributing to Monocrotaline-Induced Pulmonary Arterial Hypertension

Content Provider	Springer Nature Link
Author	Xi, Xin Liu, Shuang Shi, Hongtao Yang, Min Qi, Yongfen Wang, Jian Du, Jie
Copyright Year	2014
Abstract	Sustained inflammation is associated with pulmonary vascular remodeling and arterial hypertension (PAH). Serum–glucocorticoid regulated kinase 1 (SGK1) has been shown to participate in vascular remodeling, but its role in inflammation-associated PAH remains unknown. In this study, the importance of SGK1 expression and activation was investigated on monocrotaline (MCT)-induced PAH, an inflammation-associated experimental model of PAH used in mice and rats. The expression of SGK1 in the lungs of rats with MCT-induced PAH was significantly increased. Furthermore, SGK1 knockout mice were resistant to MCT-induced PAH and showed less elevation of right ventricular systolic pressure and right ventricular hypertrophy and showed reduced pulmonary vascular remodeling in response to MCT injection. Administering the SGK1 inhibitor, EMD638683, to rats also prevented the development of MCT-induced PAH. The expression of SGK1 was shown to take place primarily in alveolar macrophages. EMD638683 treatment suppressed macrophage infiltration and inhibited the proliferation of pulmonary arterial smooth muscle cells (PASMCs) in the lungs of rats with MCT-induced PAH. Co-culture of bone marrow-derived macrophages (BMDMs) from wild-type (WT) mice promoted proliferation of PASMC in vitro, whereas BMDMs from either SGK1 knockout mice or WT mice with EMD638683 treatment failed to induce this response. Collectively, the present results demonstrated that SGK1 is important to the regulation of macrophage activation that contributes to the development of PAH; thus, SGK1 may be a potential therapeutic target for the treatment of PAH.
Starting Page	368
Ending Page	378
Page Count	11
File Format	PDF
ISSN	15307905
Journal	Cardiovascular Toxicology
Volume Number	14
Issue Number	4
e-ISSN	15590259
Language	English
Publisher	Springer US
Publisher Date	2014-05-14
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pulmonary arterial hypertension Inflammation Serum–glucocorticoid regulated kinase 1 Pulmonary arterial smooth muscle cell Macrophage Pharmacology/Toxicology Cardiology
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Toxicology Cardiology and Cardiovascular Medicine

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Serum–Glucocorticoid Regulated Kinase 1 Regulates Macrophage Recruitment and Activation Contributing to Monocrotaline-Induced Pulmonary Arterial Hypertension