Effect of TGF-β1/SDF-1/CXCR4 signal on BM-MSCs homing in rat heart of ischemia/perfusion injury.

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.

MATERIALS AND 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.