title: Role of STIM1/Orai1-mediated store-operated Ca²⁺ entry in airway smooth muscle cell proliferation.
abstract: Hyperplasia of airway smooth muscle cells (ASMCs) is a characteristic change of chronic asthma patients. However, the underlying mechanisms that trigger this process are not yet completely understood. Store-operated Ca(2+) (SOC) entry (SOCE) occurs in response to the intracellular sarcoplasma reticulum (SR)/endoplasmic reticulum (ER) Ca(2+) store depletion. SOCE plays an important role in regulating Ca(2+) signaling and cellular responses of ASMCs. Stromal interaction molecule (STIM)1 has been proposed as an ER/SR Ca(2+) sensor and translocates to the ER underneath the plasma membrane upon depletion of the ER Ca(2+) store, where it interacts with Orai1, the molecular component of SOC channels, and brings about SOCE. STIM1 and Orai1 have been proved to mediate SOCE of ASMCs. In this study, we investigated whether STIM1/Orai1-mediated SOCE is involved in rat ASMC proliferation. We found that SOCE was upregulated during ASMC proliferation accompanied by a mild increase of STIM1 and a significant increase of Orai1 mRNA expression, whereas the proliferation of ASMCs was partially inhibited by the SOC channel blockers SKF-96365, NiCl(2), and BTP-2. Suppressing the mRNA expression of STIM1 or Orai1 with specific short hairpin RNA resulted in the attenuation of SOCE and ASMC proliferation. Moreover, after knockdown of STIM1 or Orai1, the SOC channel blocker SKF-96365 had no inhibitory effect on the proliferation of ASMCs anymore. These results suggested that STIM1/Orai1-mediated SOCE is involved in ASMC proliferation.
authors.affiliation: Division of Respiratory Medicine, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Jin-jing
authors.initials: JJ
authors.lastname: Zou
authors.forename: Ya-dong
authors.initials: YD
authors.lastname: Gao
authors.forename: Shuang
authors.initials: S
authors.lastname: Geng
authors.forename: Jiong
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D008168:Lung / Q000166:cytology / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D000071740:ORAI1 Protein; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D008562:Membrane Glycoproteins; D000071740:ORAI1 Protein; C532493:Orai1 protein, rat; C518857:Stim1 protein, rat; D000071737:Stromal Interaction Molecule 1; D002118:Calcium