Si Xiaoyun, Liu Ximing, Li Jingjing, Wu Xiaoyan
Department of Nephrology, Zhongnan Hospital of Wuhan University Wuhan 430071, Hubei Province, P. R. China.
Department of Orthopaedics Surgery, Wuhan General Hospital of Guangzhou Command Wuhan 430070, Hubei Province, P. R. China.
Int J Clin Exp Pathol. 2015 Oct 1;8(10):12368-78. eCollection 2015.
Acute ischemia reperfusion-induced kidney injury is a common cause of acute renal failure, and it is also an important cause of delayed recovery of transplanted kidney functions and even loss of function. However, there is no effective treatment method in clinical applications presently.
The objective was to investigate effects of transforming growth factor-β1 on homing of bone marrow mesenchymal stem cells in renal ischemia-reperfusion injury.
Effects of TGF-β1 over-expression in MSCs on expression of CXCR4 and chemotactic effect to SDF-1 were investigated by in vitro transmembrane chemotaxis. Anti-TGF-β1 antibody was incubated with ischemia reperfusion injury renal tissue homogenate and effects of anti-TGF-β1 antibody were observed. In addition, effects of TGF-β1 gene transfection and anti-CXCR4 antibody treatment in MSCs on expression of SDF-1/CXCR4 axis of renal tissues and damage repair were further explored.
Expression of TGF-β1 mRNA in the IRI group increased significantly, and MSCs transplantation could enhance expression of CXCR4 mRNA in rats of the IRI group, the expression of CXCR4 can be decreased by the anti-TGF-β1 antibody and the anti-CXCR4 antibody. TGF-β1 induced homing of MSCs in repair of renal ischemic reperfusion injury by regulating expression of CXCR4 on cell membranes. Blue fluorescence of DAPI-positive MSCs cells of renal parenchyma in the IRI+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 obvious than that of anti-TGF-β1 antibody.
Transforming growth factor-β1 promotes homing of bone marrow mesenchymal stem cells in renal ischemia-reperfusion injury, which will provide useful data on role of TGF-β1 in regulating SDF-1/CXCR4 axis-induced MSCs homing.
急性缺血再灌注所致肾损伤是急性肾衰竭的常见病因,也是移植肾功能延迟恢复甚至功能丧失的重要原因。然而,目前临床应用中尚无有效的治疗方法。
探讨转化生长因子-β1对肾缺血再灌注损伤中骨髓间充质干细胞归巢的影响。
采用体外跨膜趋化实验研究转化生长因子-β1在骨髓间充质干细胞中过表达对趋化因子受体4表达及对基质细胞衍生因子-1趋化作用的影响。将抗转化生长因子-β1抗体与缺血再灌注损伤肾组织匀浆孵育,观察抗转化生长因子-β1抗体的作用。此外,进一步探讨转化生长因子-β1基因转染及抗趋化因子受体4抗体处理骨髓间充质干细胞对肾组织趋化因子受体4/基质细胞衍生因子-1轴表达及损伤修复的影响。
缺血再灌注损伤组转化生长因子-β1信使核糖核酸表达显著增加,骨髓间充质干细胞移植可增强缺血再灌注损伤组大鼠趋化因子受体4信使核糖核酸表达,抗转化生长因子-β1抗体及抗趋化因子受体4抗体可降低趋化因子受体4表达。转化生长因子-β1通过调节细胞膜上趋化因子受体4的表达诱导骨髓间充质干细胞归巢参与肾缺血再灌注损伤修复。缺血再灌注损伤+骨髓间充质干细胞组肾实质中4',6-二脒基-2-苯基吲哚阳性骨髓间充质干细胞的蓝色荧光显著增强,抗转化生长因子-β1抗体及抗趋化因子受体4抗体可显著抑制其增强,抗趋化因子受体4抗体的抑制作用比抗转化生长因子-β1抗体更明显。
转化生长因子-β1促进骨髓间充质干细胞在肾缺血再灌注损伤中的归巢,这将为转化生长因子-β1在调节趋化因子受体4/基质细胞衍生因子-1轴诱导骨髓间充质干细胞归巢中的作用提供有用数据。