Stem cell factor/c-kit signaling mediated cardiac stem cell migration via activation of p38 MAPK.
OBJECTIVE
It was reported that there are cardiac stem cells (CSCs) in the rat heart, and they could reconstitute well-differentiated myocardium that are formed by blood-carrying new vessels and myocytes. However, how do the CSCs migrate into the peri-infarcted areas after myocardial infarction (MI)? It remains entirely unknown about the signal transduction involved in the migration of CSCs.


RESULTS
Rat heart MI was induced by left coronary artery ligation. Both immunohistochemical staining and Western blotting analysis was performed to detect the expression of SCF protein, and RT-PCR was conducted for the expression of SCF mRNA. Cardiac stem cells were isolated from rat hearts, and a cardiac stem cell migration assay was performed using a 48-well chemotaxis chamber system. On day 5 after MI in rats, the expression of stem cell factor (SCF) mRNA and protein was significantly increased in the peri-infarcted area, which was matched with more accumulation of CSCs in the region and improvement of cardiac function, which was blocked by p38 MAPK selective inhibitor SB203580. In in vitro experiments, SCF induced CSC migration in a concentration-dependent manner, and the antibody against SCF receptor (c-kit) blocked the SCF-induced CSC migration. Western blot analysis showed that the phosphorylated p38 MAPK (Phospho-p38 MAPK) was highly increased in the SCF-treated CSCs, and the inhibition of p38 MAPK activity significantly attenuated SCF-induced the migration of CSCs.


CONCLUSIONS
It demonstrated that SCF/c-kit signaling may mediate the migration of CSCs via activation of p38 MAPK.
Kuang
Dong
D
Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Zhao
Xia
X
Xiao
Guixiang
G
Ni
Juan
J
Feng
Youmei
Y
Wu
Renliang
R
Wang
Guoping
G
D000818:Animals; D000906:Antibodies; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000201:enzymology / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D013997:Time Factors; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000906:Antibodies; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D012333:RNA, Messenger; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580