Liu Hong-Jun, Duan Hai-Feng, Lu Zhuo-Zhuang, Wang Hua, Zhang Qun-Wei, Wu Zu-Ze, Wang Li-Sheng
Department of Experimental Hematology, Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2005 Dec;13(6):1044-8.
Hepatocyte growth factor (HGF) is one of major growth factors in the bone marrow microenvironments with which the proliferation, differentiation and migration of bone marrow-derived mesenchymal stem cells were closely contacted. However, its roles in the regulation of proliferation, differentiation and migration of bone marrow-derived mesenchymal stem cells remain unclear. This study was aimed to investigate the effect of HGF on biological characteristics of bone marrow-derived mesenchymal stem cells. Expression of c-Met, the receptor for HGF was detected by immunohistochemistry assay, cell proliferation was determined by MTT, activity of ALP was quantitatively assayed, cell migration and anoikis-induced MSC apoptosis were analyzed. The results showed that HGF not influenced the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells. Treatment of bone marrow-derived mesenchymal stem cells with recombinant human hepatocyte growth factor resulted in inhibition of anoikis-induced apoptosis. HGF significantly stimulated the migration of bone marrow-derived mesenchymal stem cells. Both PI-3 kinase and MAPK kinase were proved to be involved in HGF-induced migration. It is concluded that HGF/c-Met signal regulates the apoptosis and migration of bone marrow-derived mesenchymal stem cells.
肝细胞生长因子(HGF)是骨髓微环境中的主要生长因子之一,与骨髓间充质干细胞的增殖、分化及迁移密切相关。然而,其在调控骨髓间充质干细胞增殖、分化及迁移中的作用仍不清楚。本研究旨在探讨HGF对骨髓间充质干细胞生物学特性的影响。采用免疫组织化学法检测HGF受体c-Met的表达,MTT法检测细胞增殖,定量分析碱性磷酸酶(ALP)活性,分析细胞迁移及失巢凋亡诱导的间充质干细胞凋亡。结果显示,HGF不影响骨髓间充质干细胞的增殖和成骨分化。用重组人肝细胞生长因子处理骨髓间充质干细胞可抑制失巢凋亡诱导的细胞凋亡。HGF显著促进骨髓间充质干细胞的迁移。PI-3激酶和丝裂原活化蛋白激酶(MAPK激酶)均参与HGF诱导的迁移过程。结论:HGF/c-Met信号调节骨髓间充质干细胞的凋亡和迁移。