PMID- 24825325
OWN - NLM
STAT- MEDLINE
DCOM- 20150710
LR  - 20211203
IS  - 1559-0259 (Electronic)
IS  - 1530-7905 (Linking)
VI  - 14
IP  - 4
DP  - 2014 Dec
TI  - Serum-glucocorticoid regulated kinase 1 regulates macrophage recruitment and 
      activation contributing to monocrotaline-induced pulmonary arterial hypertension.
PG  - 368-78
LID - 10.1007/s12012-014-9260-4 [doi]
AB  - 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.
FAU - Xi, Xin
AU  - Xi X
AD  - Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
FAU - Liu, Shuang
AU  - Liu S
FAU - Shi, Hongtao
AU  - Shi H
FAU - Yang, Min
AU  - Yang M
FAU - Qi, Yongfen
AU  - Qi Y
FAU - Wang, Jian
AU  - Wang J
FAU - Du, Jie
AU  - Du J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cardiovasc Toxicol
JT  - Cardiovascular toxicology
JID - 101135818
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (RNA, Messenger)
RN  - 73077K8HYV (Monocrotaline)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (serum-glucocorticoid regulated kinase)
SB  - IM
MH  - Animals
MH  - Hypertension, Pulmonary/chemically induced/*enzymology/pathology
MH  - Immediate-Early Proteins/genetics/metabolism/*physiology
MH  - Inflammation/physiopathology
MH  - Macrophages/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Monocrotaline
MH  - Myocytes, Smooth Muscle/cytology/pathology
MH  - Protein Serine-Threonine Kinases/genetics/metabolism/*physiology
MH  - Pulmonary Artery/drug effects/pathology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Vascular Remodeling/drug effects
EDAT- 2014/05/16 06:00
MHDA- 2015/07/15 06:00
CRDT- 2014/05/15 06:00
PHST- 2014/05/15 06:00 [entrez]
PHST- 2014/05/16 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
AID - 10.1007/s12012-014-9260-4 [doi]
PST - ppublish
SO  - Cardiovasc Toxicol. 2014 Dec;14(4):368-78. doi: 10.1007/s12012-014-9260-4.