Sphingosine 1-phosphate induces alpha-smooth muscle actin expression in lung fibroblasts via Rho-kinase.
Transformation of fibroblasts into myofibroblasts is an important phenomenon that contributes to airway remodeling in bronchial asthma. Although several articles have recently indicated that a bioactive lysosphingolipid sphingosine 1-phosphate (S1P) plays roles in the pathogenesis of bronchial asthma, the role of S1P in the remodeling process is poorly understood. In the present study, we examined the effects of S1P on alpha-smooth muscle actin (SMA) expression and the morphology in lung fibroblasts. S1P stimulated the expression of alpha-SMA in a human lung fibroblast cell line WI38 that expresses EDG/S1P receptors. These processes were inhibited by Y-27632, but not by pertussis toxin. These results suggest that S1P induces a phenotypic change of lung fibroblasts via Rho-kinase that may lead to airway remodeling.
Urata
Yoshiko
Y
Division of Cardiovascular and Respiratory Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Nishimura
Yoshihiro
Y
Hirase
Tetsuaki
T
Yokoyama
Mitsuhiro
M
D000199:Actins / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D005347:Fibroblasts / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008246:Lysophospholipids / Q000502:physiology*; D009130:Muscle, Smooth / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064067:Rho Guanine Nucleotide Exchange Factors; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology; D054460:rho-Associated Kinases
C577226:ARHGEF17 protein, human; D000199:Actins; D017931:DNA Primers; D020662:Guanine Nucleotide Exchange Factors; D047908:Intracellular Signaling Peptides and Proteins; D008246:Lysophospholipids; D064067:Rho Guanine Nucleotide Exchange Factors; C060506:sphingosine 1-phosphate; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D013110:Sphingosine