Peroxisome proliferator-activated receptor γ attenuates serotonin-induced pulmonary artery smooth muscle cell proliferation and apoptosis inhibition involving ERK1/2 pathway.
Serotonin (5-HT) has been shown to be involved in pulmonary vascular remodeling in pulmonary arterial hypertension (PAH) by inducing pulmonary artery smooth muscle cells (PASMCs) proliferation and inhibiting PASMC apoptosis. Peroxisome proliferator-activated receptor γ (PPARγ) plays a crucial role in regulating proliferation and apoptosis of many cell types. Moreover, recently, loss of PPARγ has also been reported to be associated with the development of PAH. The present study is aimed to assess whether PPARγ is involved in 5-HT induced PASMC proliferation and apoptosis inhibition and the possible mechanism. We found that 5-HT could induce PASMC proliferation and inhibit PASMC apoptosis in a dose-dependent manner. Furthermore, we found that 5-HT negatively regulated PPARγ expression and gene promoter activity in PASMCs and 5-HT induced PASMC proliferation and apoptosis resistance could be abolished by PPARγ agonists and enhanced by PPARγ inhibitor. In addition, we found that extracellular signal-regulated kinase (ERK) signaling pathway mediated the 5-HT-induced inhibition of PPARγ expression. Our results might provide novel insights into the mechanisms for the pro-remodeling action of 5-HT in pulmonary vasculature.
Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
Xinyuan
X
Han
Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi, China.
Chunyan
C
Chen
Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
Gong
G
Cheng
Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
Lei
L
Liang
Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
Xiaowei
X
Yao
Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
Guang
G
Yang
Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
Penghua
P
You
Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China. Electronic address: shouxilingsyy@126.com.
Xiling
X
Shou
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D047495:PPAR gamma / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
D051017:Apoptosis Regulatory Proteins; D047495:PPAR gamma; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D012701:Serotonin; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
Apoptosis; PPARγ; Proliferation; Pulmonary artery smooth muscle cells; Serotonin