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

X Q Wang; L J Mao; Q H Fang; T Kobayashi; H J Kim; H Sugiura; S Kawasaki; S Togo; K Kamio; X Liu; S I Rennard

doi:10.1016/j.prostaglandins.2014.02.002

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

Prostaglandins Other Lipid Mediat. 2014 Jan:108:23-30. doi: 10.1016/j.prostaglandins.2014.02.002. Epub 2014 Mar 5.

Authors

X Q Wang¹, L J Mao², Q H Fang³, T Kobayashi⁴, H J Kim⁵, H Sugiura⁶, S Kawasaki⁷, S Togo⁸, K Kamio⁹, X Liu¹⁰, S I Rennard¹¹

Affiliations

¹ Pulmonary, Critical Care, Sleep and Allergy, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States; Department of Respiratory Disease, Affiliated Hospital of Hebei United University, Hebei Province, China.
² Research Center of Occupational Medicine, Peking University Third Hospital, Beijing 100191, China.
³ Department of Pulmonary and Critical Care, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
⁴ Department of Pulmonary and Critical Care Medicine, Mie University School of Medicine, Tsu, Japan.
⁵ Department of Internal Medicine, SanBon Hospital, WonKuang University School of Medicine, Seoul, South Korea.
⁶ Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
⁷ Department of Respiratory Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
⁸ Division of Respiratory Medicine, Juntendo University Faculty of Medicine & Graduate School of Medicine, Tokyo, Japan.
⁹ Department of Pulmonary Medicine/Infection and Oncology, Internal Medicine, Nippon Medical School, Tokyo, Japan.
¹⁰ Pulmonary, Critical Care, Sleep and Allergy, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States.
¹¹ Pulmonary, Critical Care, Sleep and Allergy, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States. Electronic address: srennard@unmc.edu.

PMID: 24614064
DOI: 10.1016/j.prostaglandins.2014.02.002

Abstract

Chronic airway diseases like COPD and asthma are usually accompanied with airway fibrosis. Myofibroblasts, which are characterized by expression of smooth muscle actin (α-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 α-SMA in human fetal lung fibroblast (HFL-1) and fibroblast mediated gel contraction. The results show that SPC stimulates α-SMA expression in HFL-1 and augments HFL-1 mediated collagen gel contraction in a time- and concentration-dependent manner. The α-SMA protein expression and fibroblast gel contraction induced by SPC was not blocked by TGF-β1 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 α-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.

Keywords: Fibroblast; SPC; Tissue repair.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / genetics
Actins / metabolism*
Airway Remodeling
Cells, Cultured
Collagen / metabolism
Fibroblasts / metabolism*
Gels
Humans
Lung / pathology
Phosphorylcholine / analogs & derivatives*
Receptors, Lysosphingolipid / metabolism*
Signal Transduction
Sphingosine / analogs & derivatives*
Sphingosine / physiology
Sphingosine-1-Phosphate Receptors
Transcriptional Activation
Transforming Growth Factor beta1 / physiology
rhoA GTP-Binding Protein / metabolism*

Substances

Actins
Gels
Receptors, Lysosphingolipid
S1PR2 protein, human
Sphingosine-1-Phosphate Receptors
TGFB1 protein, human
Transforming Growth Factor beta1
sphingosine phosphorylcholine
Phosphorylcholine
RHOA protein, human
Collagen
rhoA GTP-Binding Protein
Sphingosine