Osteopontin is a myosphere-derived secretory molecule that promotes angiogenic progenitor cell proliferation through the phosphoinositide 3-kinase/Akt pathway
Osteopontin is a myosphere-derived secretory molecule that promotes angiogenic progenitor cell proliferation through the phosphoinositide 3-kinase/Akt pathway
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DOI：
10.1016/j.bbrc.2007.05.104
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发表时间：
2007-07-27
影响因子：
3.1
通讯作者：
Oh, Hidemasa
中科院分区：
文献类型：
--
作者：
Ogata, Takehiro;Ueyama, Tomomi;Oh, Hidemasa
我们已经报道，骨骼肌球来源的祖细胞(MDPC)可以分化为血管细胞，MDPC移植到心肌病心脏可以改善心功能。然而，导致MDPC生长的自分泌/旁分泌分子和潜在机制尚未确定。为了探索促进MDPC增殖的分子，我们利用从MDPC中提取的RNA进行了一系列的基因表达分析和信号序列捕获方法。我们发现骨桥蛋白(OPN)是一种分泌分子，是MDPC表达最丰富的分子之一。OPN为MDPC提供了一种增殖效应。经OPN处理的MDPC显示Akt激活，抑制PI3K/Akt通路可抑制OPN的增殖作用。此外，经OPN处理的MDPC保持了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通路在调节肌源性血管生成前体细胞的增殖生长中起着重要作用。(C)2007 Elsevier Inc.保留所有权利。
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. (c) 2007 Elsevier Inc. All rights reserved.