Ogata Takehiro, Ueyama Tomomi, Nomura Tetsuya, Asada Satoshi, Tagawa Masashi, Nakamura Tomoyuki, Takahashi Tomosaburo, Matsubara Hiroaki, Oh Hidemasa
Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, Japan.
Biochem Biophys Res Commun. 2007 Jul 27;359(2):341-7. doi: 10.1016/j.bbrc.2007.05.104. Epub 2007 May 24.
We have reported that skeletal myosphere-derived progenitor cells (MDPCs) can differentiate into vascular cells, and that MDPC transplantation into cardiomyopathic hearts improves cardiac function. However, the autocrine/paracrine molecules and underlying mechanisms responsible for MDPC growth have not yet been determined. To explore the molecules enhancing the proliferation of MDPCs, we performed serial analysis of gene expression and signal sequence trap methods using RNA isolated from MDPCs. We identified osteopontin (OPN), a secretory molecule, as one of most abundant molecules expressed in MDPCs. OPN provided a proliferative effect for MDPCs. MDPCs treated with OPN showed Akt activation, and inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway repressed the proliferative effect of OPN. Furthermore, OPN-pretreated MDPCs maintained their differentiation potential into endothelial and vascular smooth muscle cells. These findings indicate an important role of OPN as an autocrine/paracrine molecule in regulating the proliferative growth of muscle-derived angiogenic progenitor cells via the PI3K/Akt pathway.
我们曾报道，骨骼肌肌球衍生祖细胞（MDPCs）可分化为血管细胞，且将MDPCs移植到患心肌病的心脏中可改善心脏功能。然而，负责MDPCs生长的自分泌/旁分泌分子及其潜在机制尚未确定。为了探索增强MDPCs增殖的分子，我们使用从MDPCs分离的RNA进行了基因表达序列分析和信号序列捕获方法。我们鉴定出骨桥蛋白（OPN），一种分泌分子，是MDPCs中表达最丰富的分子之一。OPN对MDPCs有增殖作用。用OPN处理的MDPCs显示Akt激活，抑制磷酸肌醇3激酶（PI3K）/Akt途径可抑制OPN的增殖作用。此外，经OPN预处理的MDPCs保持其向内皮细胞和血管平滑肌细胞分化的潜能。这些发现表明OPN作为一种自分泌/旁分泌分子，通过PI3K/Akt途径在调节肌肉来源的血管生成祖细胞的增殖生长中起重要作用。
