Ishisaki Akira, Hayashi Hisaki, Li Ai-Jun, Imamura Toru
Age Dimension Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan.
J Biol Chem. 2003 Jan 10;278(2):1303-9. doi: 10.1074/jbc.M207329200. Epub 2002 Nov 1.
Mouse embryonic stem-derived cells were recently shown to differentiate into endothelial and smooth muscle cells. In the present study, we investigated whether human umbilical vein endothelium-derived cells retain the potential to differentiate into smooth muscle cells. Examination of biochemical markers, including basic calponin, SM22alpha, prostaglandin E synthase, von Willebrand factor, and PECAM-1, as well as cell contractility, showed that whereas endothelium-derived cells cultured with fibroblast growth factor can be characterized as endothelial cells, when deprived of fibroblast growth factor, a significant fraction differentiates into smooth muscle-like cells. Reapplication of fibroblast growth factor reversed this differentiation. Activin A was up-regulated in fibroblast growth factor-deprived, endothelium-derived cells; moreover, the inhibitory effects of exogenous follistatin and overexpressed Smad7 on smooth muscle-like differentiation confirmed that the differentiation was driven by activin A signaling. These findings indicate that when deprived of fibroblast growth factor, human umbilical vein endothelium-derived cells are capable of differentiating into smooth muscle-like cells through activin A-induced, Smad-dependent signaling, and that maintenance of the endothelial cell phenotype and differentiation into smooth muscle-like cells are reciprocally controlled by fibroblast growth factor-1 and activin A.
小鼠胚胎干细胞衍生细胞最近被证明可分化为内皮细胞和平滑肌细胞。在本研究中，我们调查了人脐静脉内皮衍生细胞是否保留分化为平滑肌细胞的潜力。对包括碱性钙调蛋白、SM22α、前列腺素E合酶、血管性血友病因子和PECAM-1在内的生化标志物以及细胞收缩性的检测表明，在用成纤维细胞生长因子培养时，内皮衍生细胞可被表征为内皮细胞，而当缺乏成纤维细胞生长因子时，相当一部分细胞会分化为平滑肌样细胞。重新应用成纤维细胞生长因子可逆转这种分化。在缺乏成纤维细胞生长因子的内皮衍生细胞中，激活素A上调；此外，外源性卵泡抑素和过表达的Smad7对平滑肌样分化的抑制作用证实，这种分化是由激活素A信号驱动的。这些发现表明，当缺乏成纤维细胞生长因子时，人脐静脉内皮衍生细胞能够通过激活素A诱导的、Smad依赖的信号通路分化为平滑肌样细胞，并且内皮细胞表型的维持和平滑肌样细胞的分化受成纤维细胞生长因子-1和激活素A的相互调控。
