title: Ischaemia/reperfusion induced cardiac stem cell homing to the injured myocardium by stimulating stem cell factor expression via NF-kappaB pathway.
abstract: Ischaemia/reperfusion (I/R) is a major cause of heart failure. Recently cardiac stem cells (CSCs) were proposed as the most appropriate cell type for heart disease therapy. However, it is still unclear whether I/R can stimulate the CSCs homing to the injured myocardium. Male Sprague-Dawley rats were subjected to a 30-min ischaemia followed by reperfusion of different intervals. RT-PCR, western blotting and immunohistochemistry were performed to detect stem cell factor (SCF) expression at mRNA and protein levels respectively. Activation of nuclear factor-kappaB (NF-kappaB) was determined by electrophoretic mobility shift assay. To assess the homing of CSCs in vivo, BrdU-labelled CSCs were injected into AV-groove before induction of ischaemia and examined by immunofluorescent staining in the injured myocardium after I/R. From day 3 to day 6 after reperfusion, the accumulation of CSCs was significantly elevated in the injured area, which was matched with the increased SCF expression during I/R. Pretreatment of rats with NF-kappaB inhibitor, N-acetyl-L-cysteine (NAC) not only suppressed NF-kappaB activation induced by I/R but also attenuated SCF expression. Further analysis revealed that I/R induced phosphorylation of IkappaBalpha after 15 min of reperfusion, and the raised phosphor-IkappaBalpha returned to the basal level at 2 h of reperfusion. In simulated I/R(SI/R) in vitro, it enhanced NF-kappaB activation and SCF expression in cultured neonatal rat cardiomyocytes, which was markedly inhibited by NF-kappaB decoy oligodeoxynucleotide or NAC. Taken together, our results demonstrated that I/R induced CSCs homing to the injured myocardium by stimulating myocardial SCF expression via activation of NF-kappaB.
authors: Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Junli
authors: J
authors: Guo
authors: Wei
authors: W
authors: Jie
authors: Dong
authors: D
authors: Kuang
authors: Juan
authors: J
authors: Ni
authors: Duoen
authors: D
authors: Chen
authors: Qilin
authors: Q
authors: Ao
authors: Guoping
authors: G
authors: Wang
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology; D019089:Stem Cell Factor / Q000378:metabolism* / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*; D016277:Ventricular Function, Left
chemical_list: D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D019089:Stem Cell Factor; D000072000:NF-KappaB Inhibitor alpha