趋化因子-8对高糖环境下脂肪间充质干细胞迁移能力的影响

Effect of chemokine-8 factor on the migration ability of human adipose derived mesenchymal stem cell in high glucose environment

目的探讨高糖环境下,趋化因子-8(CXCL-8)对人脂肪间充质干细胞(h ADMSCs)迁移能力的影响和机制。方法建立高糖环境模型;在高糖条件下,建立CXCL-8实验组、Akt抑制剂组和高糖对照组,在正常条件培养的h ADMSCs为正常对照组;分别用细胞划痕实验、Transwell细胞小室实验检测CXCL-8对h ADMSCs的迁移能力影响,并用Western blotting、ELISA实验检测Akt、信号转导和转录激活因子(STAT3)和血管内皮生长因子(VEGF)等蛋白表达。结果相对高糖对照组,CXCL-8实验组h ADMSCs细胞划痕面积闭合率和Transwell细胞小室迁移率均增高(P<0.01);而Akt抑制剂组h ADMSCs细胞划痕面积闭合率或Transwell细胞小室迁移率比CXCL-8实验组皆降低(P<0.01);CXCL-8实验组磷酸化Akt、m TOP、STAT3蛋白表达增高,CXCL-8实验组上清液的VEGF、表皮细胞生长因子(EGF)含量明显增高(P<0.01);而Akt抑制剂组h ADMSCs分泌能力下降(P<0.01)。结论高糖环境下,CXCL-8通过Akt-STAT3通路促进间充质干细胞(MSCs)旁分泌VEGF等因子,促进MSCs迁移,对招募宿主细胞归巢,促进组织损伤修复具有重要意义。

Objective To investigate the effect of chemokines （CXCL）-8 factor on the chemotaxis ability of human adipose-derived mesenchymal stem cells （hADMSCs）. Methods The animals under the high glucose environment were divided into CXCL-8 experimental group, Akt inhibitor group and control group of high glucose. The normal control group was the cultural hADMSCs under the normal condition. Cell scratch, Transwells cell chamber experiment were used to check the effect of chemotaxis ability of CXCL-8 on the ADMSCs Western blotting, and ELISA experiment to check the protein expression of Akt, signal transducer and activator of transcription 3 （STAT3） and vascular endothelial growth factor （VEGF）. Results Compared with the control group, the closing rate of hADMSCs cell scratch area in CXCL-8 experimental group and migration rate of Transwell cell chamber were increased （ P 〈 0.01 ）. The closing rate of cell scratch area in Akt inhibitor group and migration rate were decreased （P 〈 0.01 ）. The protein expressions of phosphorylated Akt, mTOP and STAT3 were increased. The VEGF, epidermal growth factor （EGF） of liquid supernatant in CXCL-8 experimental group were increased significantly （ P 〈 0.01 ） ; but the secretion ability of Akt inhibitor group was decreased （P 〈0.01 ）. Conclusion Under the high glucose environment, the CXCL-8 promoted MSCs paracrine VEGF factors through Akt-STAT3 pathway and promoted migration of MSCs, which may have the important meaning for recruit host cell homing and promote damage repair.