title: Knockdown of stromal interaction molecule 1 attenuates hepatocyte growth factor-induced endothelial progenitor cell proliferation.
abstract: Increased Ca(2+) entry through store-operated Ca(2+) channels (SOCCs) plays an essential role in the regulation of hepatocyte growth factor (HGF)-induced cell proliferation. Stromal interaction molecule 1 (STIM1) is thought to transmit endoplasmic reticulum (ER) Ca(2+) store depletion signals to the plasma membrane (PM), causing the opening of SOCCs in the PM. However, the relationship between HGF and STIM1 in endothelial progenitor cell (EPC) proliferation remains uncharacterized. The objective of this study was to evaluate the potential involvement of STIM1 in HGF-induced EPC proliferation. For this purpose, we used cultured rat bone marrow-derived EPCs and found that HGF-induced EPC proliferation at low concentrations. Store-operated Ca(2+) entry (SOCE) was elevated in HGF-treated EPCs, and the SOCC inhibitors 2-aminoethoxydiphenyl borate (2-APB) and BTP-2 inhibited the HGF-induced proliferation response. Moreover, STIM1 mRNA and protein expression levels were increased in response to HGF stimulation and knockdown of STMI1 decreased SOCE and prevented HGF-induced EPC proliferation. In conclusion, our data suggest that HGF-induced EPC proliferation is mediated partly via activation of STIM1.
authors.affiliation: Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Yankun
authors.initials: Y
authors.lastname: Shi
authors.forename: Mingbao
authors.initials: M
authors.lastname: Song
authors.forename: Ruiwei
authors.initials: R
authors.lastname: Guo
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Pan
authors.initials: P
authors.lastname: Gao
authors.forename: Weibin
authors.initials: W
authors.lastname: Shi
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology*; D000071737:Stromal Interaction Molecule 1; D013830:Thiadiazoles / Q000494:pharmacology
chemical_list: C476308:4-methyl-4'-(3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl)-1,2,3-thiadiazole-5-carboxanilide; D000813:Anilides; D001896:Boron Compounds; D008562:Membrane Glycoproteins; C518857:Stim1 protein, rat; D000071737:Stromal Interaction Molecule 1; D013830:Thiadiazoles; D017228:Hepatocyte Growth Factor; C109986:2-aminoethoxydiphenyl borate; D002118:Calcium