Sphingosylphosphorylcholine induces α-smooth muscle actin expression in human lung fibroblasts and fibroblast-mediated gel contraction via S1P2 receptor and Rho/Rho-kinase pathway

被引:16
|
作者
Wang, X. Q. [1 ,2 ]
Mao, L. J. [3 ]
Fang, Q. H. [4 ]
Kobayashi, T. [5 ]
Kim, H. J. [6 ]
Sugiura, H. [7 ]
Kawasaki, S. [8 ]
Togo, S. [9 ,10 ]
Kamio, K. [11 ]
Liu, X. [1 ]
Rennard, S. I. [1 ]
机构
[1] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE 68198 USA
[2] Hebei United Univ, Affiliated Hosp, Dept Resp Dis, Tangshan, Hebei Province, Peoples R China
[3] Peking Univ, Hosp 3, Res Ctr Occupat Med, Beijing 100191, Peoples R China
[4] Capital Med Univ, Beijing Shijitan Hosp, Dept Pulm & Crit Care, Beijing 100038, Peoples R China
[5] Mie Univ, Sch Med, Dept Pulm & Crit Care Med, Tsu, Mie 514, Japan
[6] WonKuang Univ, Sch Med, SanBon Hosp, Dept Internal Med, Seoul, South Korea
[7] Tohoku Univ, Grad Sch Med, Dept Resp Med, Aoba Ku, Sendai, Miyagi 9808574, Japan
[8] Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan
[9] Juntendo Univ, Fac Med, Div Resp Med, Tokyo, Japan
[10] Grad Sch Med, Tokyo, Japan
[11] Nippon Med Sch, Dept Pulm Med Infect & Oncol, Tokyo 113, Japan
关键词
SPC; Tissue repair; Fibroblast; SPHINGOSINE; 1-PHOSPHATE; RHO GTPASES; MYOFIBROBLAST; MIGRATION; GROWTH; RAC;
D O I
10.1016/j.prostaglandins.2014.02.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Chronic airway diseases like COPD and asthma are usually accompanied with airway fibrosis. Myofibroblasts, which are characterized by expression of smooth muscle actin (alpha-SMA), play an important role in a variety of developmental and pathological processes, including fibrosis and wound healing. Sphingosylphosphorylcholine (SPC), a sphingolipid metabolite, has been implicated in many physiological and pathological conditions. The current study tested the hypothesis that SPC may modulate tissue remodeling by affecting the expression of a-SMA in human fetal lung fibroblast (HFL-1) and fibroblast mediated gel contraction. The results show that SPC stimulates a-SMA expression in HFL-1 and augments HFL-1 mediated collagen gel contraction in a time- and concentration-dependent manner. The a-SMA protein expression and fibroblast gel contraction induced by SPC was not blocked by TGF-beta 1 neutralizing antibody: However, it was significantly blocked by S1P2 receptor antagonist JTE-013, the Rho-specific inhibitor C3 exoenzyme, and a Rho-kinase inhibitor Y-27632. These findings suggest that SPC stimulates a-SMA protein expression and HFL-1 mediated collagen gel contraction via S1P2 receptor and Rho/Rho kinase pathway, and by which mechanism, SPC may be involved in lung tissue remodeling. (c) 2014 Published by Elsevier Inc.
引用
收藏
页码:23 / 30
页数:8
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