Knockdown of stromal interaction molecule 1 attenuates hepatocyte growth factor-induced endothelial progenitor cell proliferation.
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.
Shi
Yankun
Y
Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Song
Mingbao
M
Guo
Ruiwei
R
Wang
Hong
H
Gao
Pan
P
Shi
Weibin
W
Huang
Lan
L
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
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