title: Sphingosylphosphorylcholine induces α-smooth muscle actin expression in human lung fibroblasts and fibroblast-mediated gel contraction via S1P2 receptor and Rho/Rho-kinase pathway.
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.
authors.affiliation: 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.
authors.forename: X Q
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Research Center of Occupational Medicine, Peking University Third Hospital, Beijing 100191, China.
authors.forename: L J
authors.initials: LJ
authors.lastname: Mao
authors.affiliation: Department of Pulmonary and Critical Care, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
authors.forename: Q H
authors.initials: QH
authors.lastname: Fang
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Mie University School of Medicine, Tsu, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Internal Medicine, SanBon Hospital, WonKuang University School of Medicine, Seoul, South Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sugiura
authors.affiliation: Department of Respiratory Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kawasaki
authors.affiliation: Division of Respiratory Medicine, Juntendo University Faculty of Medicine & Graduate School of Medicine, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Togo
authors.affiliation: Department of Pulmonary Medicine/Infection and Oncology, Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kamio
authors.affiliation: Pulmonary, Critical Care, Sleep and Allergy, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Pulmonary, Critical Care, Sleep and Allergy, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States. Electronic address: srennard@unmc.edu.
authors.forename: S I
authors.initials: SI
authors.lastname: Rennard
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D056151:Airway Remodeling; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005782:Gels; D006801:Humans; D008168:Lung / Q000473:pathology; D010767:Phosphorylcholine / Q000031:analogs & derivatives*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology; D000081025:Sphingosine-1-Phosphate Receptors; D015533:Transcriptional Activation; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D005782:Gels; D049349:Receptors, Lysosphingolipid; C477522:S1PR2 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; C066737:RHOA protein, human; D003094:Collagen; D020742:rhoA GTP-Binding Protein; D013110:Sphingosine
keywords: Fibroblast; SPC; Tissue repair