Differential regulation of airway smooth muscle cell migration by e-prostanoid receptor subtypes

Hiromichi Aso, Satoru Ito, Akemi Mori, Nobukazu Suganuma, Masataka Morioka, Norihiro Takahara, Masashi Kondo, Yoshinori Hasegawa

研究成果: Article

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Migration of airway smooth muscle (ASM) cells plays an important role in the pathophysiology of airway hyperresponsiveness and remodeling in asthma. It has been reported that prostaglandin (PG)E2 inhibits migration of ASM cells. Although PGE2 regulates cellular functions via binding to distinct prostanoid EP receptors, the role of EP receptor subtypes in mechanisms underlying cell migration has not been fully elucidated. We investigated the role of EP receptors in the inhibitory effects of PGE2 on the migration ofhuman ASM cells. Migration induced by platelet-derived growth factor (PDGF)-BB (10 ng/ml, 6 h) was assessed by a chemotaxis chamber assay. PDGF-BB-induced cell migration was inhibited by PGE2, the specific EP2 agonist ONO-AE1-259-01, the specific EP4 agonist ONO-AE1-329, and cAMP-mobilizing agents. The inhibition of cell migration by PGE2 was significantly reversed by a blockade of EP2 and EP4 receptors using antagonists or transfection with siRNAs. Moreover, PGE2, the EP2 agonist, and the EP4 agonist significantly increased phosphorylation of small heat shock protein 20, one of the protein substrates for protein kinaseA(PKA), with depolymerization of actin. In contrast, the EP3 agonist ONO-AE-248 significantly promoted baseline cell migration without affecting PDGF-BB-induced cell migration. In summary, activation of EP2 and EP4 receptors and subsequent activation of the cAMP/PKA pathway are the main mechanisms of inhibition of ASMcellmigration by PGE2. HSP20 phosphorylation by PKAis possibly involved in thismechanism.Conversely, EP3 is potent in promoting cell migration. EP receptor subtypes may be novel therapeutic targetmolecules in airway remodeling and asthma.

元の言語English
ページ(範囲)322-329
ページ数8
ジャーナルAmerican Journal of Respiratory Cell and Molecular Biology
48
発行部数3
DOI
出版物ステータスPublished - 01-03-2013

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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