stim1 regulates platelet-derived growth factor-induced migration and ca2+ influx in human airway smooth muscle cellsstim1调节血小板源生长因素的迁移和ca2 +涌入人类气管平滑肌细胞.pdfVIP

STIM1 Regulates Platelet-Derived Growth Factor-Induced Migration and Ca2+ Influx in Human Airway Smooth Muscle Cells 1. 1 . 1 1 1 Nobukazu Suganuma , Satoru Ito * , Hiromichi Aso , Masashi Kondo , Mitsuo Sato , Masahiro Sokabe2, Yoshinori Hasegawa1 1 Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan, 2 Department of Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan Abstract 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+] ) regulate most ASM cell functions related to i 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+] followed by sustained [Ca2+] elevation. Sustained increases in [Ca2+] i i