@phdthesis{oai:nagoya.repo.nii.ac.jp:00016789,
 author = {Suganuma, Nobukazu and Ito, Satoru and Aso, Hiromichi and Kondo, Masashi and Sato, Mitsuo and Sokabe, Masahiro and Hasegawa, Yoshinori},
 month = {Sep},
 note = {It is suggested that migration of airway smooth muscle (ASM) cells plays an important role in the pathogenesis of airway remodeling in asthma. Increases in intracellular Ca2+ concentrations ([Ca2+]i) regulate most ASM cell functions related to asthma, such as contraction and proliferation. Recently, STIM1 was identified as a sarcoplasmic reticulum (SR) Ca2+ sensor that activates Orai1, the Ca2+ channel responsible for store-operated Ca2+ entry (SOCE). We investigated the role of STIM1 in [Ca2+]i and cell migration induced by platelet-derived growth factor (PDGF)-BB in human ASM cells. Cell migration was assessed by a chemotaxis chamber assay. Human ASM cells express STIM1, STIM2, and Orai1 mRNAs. SOCE activated by thapsigargin, an inhibitor of SR Ca2+-ATPase, was significantly blocked by STIM1 siRNA and Orai1 siRNA but not by STIM2 siRNA. PDGF-BB induced a transient increase in [Ca2+]i followed by sustained [Ca2+]i elevation. Sustained increases in [Ca2+]i due to PDGF-BB were significantly inhibited by a Ca2+ chelating agent EGTA or by siRNA for STIM1 or Orai1. The numbers of migrating cells were significantly increased by PDGF-BB treatment for 6 h. Knockdown of STIM1 and Orai1 by siRNA transfection inhibited PDGF-induced cell migration. Similarly, EGTA significantly inhibited PDGF-induced cell migration. In contrast, transfection with siRNA for STIM2 did not inhibit the sustained elevation of [Ca2+]i or cell migration induced by PDGF-BB. These results demonstrate that STIM1 and Orai1 are essential for PDGF-induced cell migration and Ca2+ influx in human ASM cells. STIM1 could be an important molecule responsible for airway remodeling., 名古屋大学博士学位論文 学位の種類 : 博士(医学)(課程) 学位授与年月日:平成25年3月25日 菅沼伸一氏の博士論文として提出された},
 school = {名古屋大学, Nagoya University},
 title = {STIM1 Regulates Platelet-Derived Growth Factor-Induced Migration and Ca2+ Influx in Human Airway Smooth Muscle Cells},
 year = {2012}
}