Department of Cardiovascular Surgery, Fuwai Hospital, CAMS and PUMC, Beijing, China.
Eur Rev Med Pharmacol Sci. 2016 Mar;20(5):899-905.
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.
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.
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.
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.
心肌缺血/再灌注（I/R）损伤是心力衰竭的常见原因。然而，目前尚无有效的治疗方法。本研究旨在探讨转化生长因子-β1（TGF-β1）对骨髓间充质干细胞（MSC）在心肌 I/R 损伤中归巢的影响。
通过体外跨膜趋化性研究 TGF-β1 对 MSC 中 CXCR4[趋化因子（C-X-C 基序）受体 4]表达和对 SDF-1（基质细胞衍生因子 1）的趋化作用的影响。用抗 TGF-β1 孵育小鼠 I/R 损伤的心脏组织。此外，进一步探讨 TGF-β1 和抗 CXCR4 处理 MSC 对心脏组织中 SDF-1/CXCR4 表达及 I/R 损伤修复的影响。
TGF-β1 处理后 MSC 中 CXCR4 和 TGF-β1 表达明显增加；TGF-β1 处理增加了 MSC 细胞迁移，抗 CXCR4 和抗 TGF-β1 处理阻断了 MSC/TGF-β1 细胞迁移。小鼠 I/R 损伤心肌组织中 TGF-β1 表达增加，MSC 移植可增强小鼠 I/R 损伤心肌组织中 CXCR4 的蛋白表达，抗 TGF-β1 和抗 CXCR4 处理可降低 CXCR4 的表达。TGF-β1 通过调节细胞膜上 CXCR4 的表达诱导 MSC 归巢修复心肌损伤。I/R+MSC 组心肌中 DAPI 阳性 MSC 细胞的蓝色荧光明显增强，抗 TGF-β1 和抗 CXCR4 抗体明显抑制，抗 CXCR4 抗体的抑制作用强于抗 TGF-β1 抗体。
TGF-β1 促进 I/R 损伤心肌中骨髓（BM）MSC 的归巢。该研究为 TGF-β1 在调节 SDF-1/CXCR4 轴诱导 MSC 归巢中的作用提供了有用的数据。
