Clusterin induces CXCR4 expression and migration of cardiac progenitor cells.
Clusterin (CST) is a stress-responding protein with multiple biological functions, including the inhibition of apoptosis and inflammation and transport of lipids. It may also participate in cell traffic and migration. In the process of post-infarct cardiac tissue repair, stem cells migrate into the damaged myocardium under the influence of chemoattractive substances such as stromal cell-derived factor (SDF). This study aimed at testing whether CST enhances expression of stem cell homing receptor and migration of cardiac progenitor cells (CPCs). CPCs isolated from fetal canine hearts transduced by CST cDNA expressed high levels of CXCR4, a receptor for SDF-1. The transfected cells also showed an increased migratory response to SDF-1 stimulation. The SDF-1-mediated migration of the CST-expressing CPCs was attenuated by PI3 kinase inhibitor LY294002 but not by mitogen-activated protein/ERK kinase inhibitor PD98059. Analysis of cell cycle by flow cytometry revealed no significant difference in cell cycle between the transduced and control CPCs. Thus, CST expression may increase CPCs migration via increasing CXCR4 expression and SDF-1/chemokine receptor signaling in a PI3/Akt-dependent manner.
Li
Yangxin
Y
Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, TX 77030, USA. yangxin_li@yahoo.com
Qu
Jiangbo
J
Shelat
Harnath
H
Gao
Song
S
Wassler
Michael
M
Geng
Yong-Jian
YJ
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D002453:Cell Cycle / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000494:pharmacology; D051152:Clusterin / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005333:Fetus / Q000166:cytology; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D009206:Myocardium / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D014162:Transfection
D000906:Antibodies; D054377:Chemokine CXCL12; D051152:Clusterin; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D019718:Receptors, CXCR4