PMID- 14656985 OWN - NLM STAT- MEDLINE DCOM- 20040106 LR - 20120215 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 17 IP - 15 DP - 2003 Dec TI - Cardiomyocytes overexpressing TNF-alpha attract migration of embryonic stem cells via activation of p38 and c-Jun amino-terminal kinase. PG - 2231-9 AB - Tumor necrosis factor-alpha (TNF-alpha) plays an important role in the pathogenesis of myocardial infarction. Stem cells are able to regenerate infarcted myocardium. This study investigated whether TNF-alpha was able to induce migration of embryonic stem cells (ESCs) in vitro. We used a Transwell assay in which neonatal rat cardiomyocytes, with or without transfection of TNF-alpha cDNA, were plated in the lower compartments and mouse ESCs tagged with green fluorescent protein were added to the upper compartments. TNF-alpha level was significantly increased in the medium of the lower compartments seeded with TNF-alpha-transfected cardiomyocytes. Compared with the controls, overexpression of TNF-alpha significantly enhanced migration of ESCs to the lower compartments. This enhancement was attenuated by preincubation of ESCs with the antibody against the type II TNF-alpha receptor (TNF-RII), but not by the antibody against the type I TNF-alpha receptor (TNF-RI). Western blot analysis showed that the phosphorylated protein levels of p38 and c-Jun amino-terminal kinase (JNK) were significantly increased in TNF-alpha-treated ESCs. Inhibition of the activity of p38 or JNK significantly attenuated TNF-alpha-induced ESC migration. Our data demonstrate that excessive TNF-alpha stimulates TNF-RII and enhances migration of ESCs in vitro. Activation of p38 and JNK is required for TNF-alpha-enhanced ESC migration. FAU - Chen, Yu AU - Chen Y AD - Stem Cells Research Laboratory, The Charles A. Dana Research Institute and Harvard-Thorndike Laboratory, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. FAU - Ke, Qingen AU - Ke Q FAU - Yang, Yinke AU - Yang Y FAU - Rana, Jamal S AU - Rana JS FAU - Tang, Jian AU - Tang J FAU - Morgan, James P AU - Morgan JP FAU - Xiao, Yong-Fu AU - Xiao YF LA - eng GR - DA11762/DA/NIDA NIH HHS/United States GR - DA12774/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Cell Communication MH - Cell Movement MH - Cells, Cultured MH - Embryo, Mammalian/*cytology MH - Enzyme Activation MH - JNK Mitogen-Activated Protein Kinases MH - MAP Kinase Signaling System MH - Mitogen-Activated Protein Kinases/*metabolism MH - Myocytes, Cardiac/*metabolism/physiology MH - Rats MH - Receptors, Tumor Necrosis Factor/physiology MH - Stem Cells/enzymology/*physiology MH - Transfection MH - Tumor Necrosis Factor-alpha/genetics/metabolism/*physiology MH - p38 Mitogen-Activated Protein Kinases EDAT- 2003/12/06 05:00 MHDA- 2004/01/07 05:00 CRDT- 2003/12/06 05:00 PHST- 2003/12/06 05:00 [pubmed] PHST- 2004/01/07 05:00 [medline] PHST- 2003/12/06 05:00 [entrez] AID - 17/15/2231 [pii] AID - 10.1096/fj.03-0030com [doi] PST - ppublish SO - FASEB J. 2003 Dec;17(15):2231-9. doi: 10.1096/fj.03-0030com.