Li Tao-Sheng, Komota Takahiro, Ohshima Mako, Qin Shu-Lan, Kubo Masayuki, Ueda Kazuhiro, Hamano Kimikazu
Department of Surgery and Clinical Science, Yamaguchi University, Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505, Japan.
Biochem Biophys Res Commun. 2008 Feb 22;366(4):1074-80. doi: 10.1016/j.bbrc.2007.12.095. Epub 2007 Dec 26.
Transforming growth factor-beta(1) (TGF-beta(1)) was found to induce the myogenic differentiation of bone marrow stem cells (BMSC). We investigated the morphological and electrophysiological properties of differentiated cells, and the mechanisms related to TGF-beta(1)-induced myogenic differentiation. We found that TGF-beta increased the expression of the cardiac transcription factors, GATA-4 and NKx-2.5, in BMSC after 1-3 days of cultivation. TGF-beta also induced the expressions of cardiac myosin, troponins, and ANP after 3-14 days of cultivation. However, the Ca(2+) transient was relatively weak, the connexin-43 expression was irregular, and spontaneous beating was not detected within 28 days observation. TGF-beta stimulation up-regulated most of the TGF-beta BMP signaling pathway genes, including TGFBI, ACVR2B, and phosphorylated Smad-2 and Smad-3, within 24h. TGF-beta induced the differentiation of BMSC into immature cardiomyocytes by activating the TGF-beta BMP signaling pathway.
发现转化生长因子-β1（TGF-β1）可诱导骨髓干细胞（BMSC）发生肌源性分化。我们研究了分化细胞的形态和电生理特性，以及与TGF-β1诱导的肌源性分化相关的机制。我们发现，培养1-3天后，TGF-β可增加BMSC中心脏转录因子GATA-4和NKx-2.5的表达。培养3-14天后，TGF-β还可诱导心肌肌球蛋白、肌钙蛋白和心钠肽的表达。然而，Ca(2+)瞬变相对较弱，连接蛋白-43表达不规则，且在28天的观察期内未检测到自发搏动。TGF-β刺激在24小时内上调了大多数TGF-β BMP信号通路基因，包括TGFBI、ACVR2B以及磷酸化的Smad-2和Smad-3。TGF-β通过激活TGF-β BMP信号通路诱导BMSC分化为未成熟心肌细胞。
