title: Effect of TGF-β1/SDF-1/CXCR4 signal on BM-MSCs homing in rat heart of ischemia/perfusion injury.
abstract: OBJECTIVE
  Heart ischemia/reperfusion (I/R) injury is a common cause of heart failure. However, there is no effective method to treat the disease presently. The present research was to investigate the effects of transforming growth factor-β1 (TGF-β1) on homing of bone marrow mesenchymal stem cells (MSC) in heart I/R injury.
  
  
  METHODS
  Effects of TGF-β1 on the expression of CXCR4 [Chemokine (C-X-C Motif) Receptor 4] and chemotactic effect to SDF-1 (stromal cell-derived factor 1) in MSCs were investigated by in vitro transmembrane chemotaxis. Anti-TGF-β1 was incubated with I/R injury's heart tissue of mice. In addition, effects of TGF-β1 and anti-CXCR4 treatment using MSCs on the expression of SDF-1/CXCR4 in heart tissue and on I/R injury repair were further explored.
  
  
  RESULTS
  CXCR4 and TGF-β1 expression were significantly increased after TGF-β1 treatment in MSCs; TGF-β1 treatment increased MSCs cell migration, and anti-CXCR4 and anti-TGF-β1 treatment blocked MSCs/TGF-β1cell migration. Expression of TGF-β1 in the I/R injury's myocardial tissue of mice was increased, and MSCs transplantation could enhance the protein expression of CXCR4 in the I/R injury's myocardial tissue of mice, and the expression of CXCR4 was decreased by the anti-TGF-β1 and the anti-CXCR4 treatment. TGF-β1 induced homing of MSCs in the repair of myocardial injury by regulating expression of CXCR4 on the cell membranes. Blue fluorescence of DAPI-positive MSCs cells of myocardial in the I/R+MSC group was enhanced significantly, which was significantly inhibited by anti-TGF-β1 and anti-CXCR4 antibody, and the inhibitory effect of anti-CXCR4 antibody was more evident than that of anti-TGF-β1 antibody.
  
  
  CONCLUSIONS
  TGF-β1 promotes homing of bone marrow (BM) MSCs in I/R injury's myocardial. The study provided useful data on the role of TGF-β1 in regulating SDF-1/CXCR4 axis-induced MSCs homing.
authors.affiliation: Department of Cardiovascular Surgery, Fuwai Hospital, CAMS and PUMC, Beijing, China. yszxyyfcy@126.com.
authors.forename: S-J
authors.initials: SJ
authors.lastname: Zhang
authors.forename: X-Y
authors.initials: XY
authors.lastname: Song
authors.forename: M
authors.initials: M
authors.lastname: He
authors.forename: S-B
authors.initials: SB
authors.lastname: Yu
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000502:physiology; D006321:Heart / Q000187:drug effects; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology* / Q000502:physiology
chemical_list: C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D019718:Receptors, CXCR4; D053773:Transforming Growth Factor beta1