Serotonin drives the activation of pulmonary artery adventitial fibroblasts and TGF-β1/Smad3-mediated fibrotic responses through 5-HT2A receptors

被引：3
作者：
Chunyan Chen
Xinyuan Han
Fenling Fan
Ya Liu
Tingzhong Wang
Juanjuan Wang
Peijing Hu
Aiqun Ma
Hongyan Tian
机构：
[1] First Affiliated Hospital of the Medical College,Department of Cardiovascular Medicine
[2] Xi’an Jiaotong University,Department of Cardiology
[3] Shaanxi Provincial People’s Hospital,undefined
来源：
Molecular and Cellular Biochemistry | 2014年 / 397卷
关键词：
Serotonin; Activation; Pulmonary artery adventitial fibroblasts; TGF-β1/Smad3;
D O I：
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学科分类号：
摘要：
Pulmonary arterial remodeling is characterized by excessive proliferation, migration, and pro-differentiation and fibrotic activation of adventitial fibroblasts in pulmonary arterial hypertension (PAH) process. Several lines of evidence indicate that serotonin (5-HT) plays a central role in the pathogenesis of pulmonary arterial remodeling. In the present study, we investigated whether 5-HT is directly involved in the functional regulation of pulmonary artery adventitial fibroblasts (PAFs). Incubation of cultured rat PAFs with 5-HT caused a dose-dependent stimulation of cell proliferation, migration activity, and a time-dependent increase of α-SMA expression, a marker of fibroblast differentiation into myofibroblasts, and adventitia fibrosis, evaluating connective tissue growth factor (CTGF) and extracellular matrix (ECM) mRNAs and proteins. These effects were attenuated by the 5-HT2A receptor antagonist, ketanserin and mimicked by the 5-HT2A receptor agonist DOI. 5-HT-induced fibroblasts phenotypic alterations and ECM accumulation were dependent on stimulation of transforming growth factor (TGF)-β1 as demonstrated using a neutralizing antibody. 5-HT also caused Smad3 phosphorylation and ketanserin diminished 5-HT-induced Smad3 activation. These results demonstrated that 5-HT can directly activate PAFs through 5-HT2A receptor and promote fibroblasts phenotypic alterations and adventitia fibrosis depending on the signaling of the TGF-β1/Smad3 pathway.
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页码：267 / 276
页数：9
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共 176 条
  • [1] Taguchi K(2013)Unlooked-for significance of cardiac versus vascular effects of endothelin-1 in the pathophysiology of pulmonary arterial hypertension Circ Res 112 227-229
  • [2] Hattori Y(2013)Vascular remodeling in pulmonary hypertension J Mol Med (Berl) 91 297-309
  • [3] Shimoda LA(2004)Cellular and molecular pathobiology of pulmonary arterial hypertension J Am Coll Cardiol 43 13S-24S
  • [4] Laurie SS(2013)The adventitia: essential regulator of vascular wall structure and function Annu Rev Physiol 75 23-47
  • [5] Humbert M(2006)Role of the adventitia in pulmonary vascular remodeling Physiology 21 134-145
  • [6] Morrell NW(2011)The vascular adventitia: its role in the arterial injury response Vasc Endovasc Surg 45 381-390
  • [7] Archer SL(2014)MicroRNA-124 controls the proliferative, migratory, and inflammatory phenotype of pulmonary vascular fibroblasts Circ Res 114 67-78
  • [8] Stenmark KR(2009)The expanded biology of serotonin Annu Rev Med 60 355-366
  • [9] MacLean MR(1995)Increased plasma serotonin in primary pulmonary hypertension Am J Med 99 249-254
  • [10] Lang IM(2000)High plasma serotonin levels in primary pulmonary hypertension. Effect of long-term epoprostenol (prostacyclin) therapy Arterioscler Thromb Vasc Biol 20 2233-2239
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