Mechanical strain activates a program of genes functionally involved in paracrine signaling of angiogenesis.
Mechanical strain activates a program of genes functionally involved in paracrine signaling of angiogenesis.
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DOI：
10.1152/physiolgenomics.90291.2008
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发表时间：
2008-12
影响因子：
4.6
通讯作者：
Rude Yang;J. Amir;Haibo Liu;B. Chaqour
中科院分区：
文献类型：
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作者：
Rude Yang;J. Amir;Haibo Liu;B. Chaqour
进行研究以检查机械刺激在体外和体内介导膀胱细胞中血管生成控制的程度。对照非拉伸和周期性拉伸膀胱平滑肌细胞之间的差异基因表达进行了评估，使用寡核苷酸微阵列和网络工具快速分配和信息传递（FSTGO）的途径分析。数据显示，相当一部分（86个中的33个）的机械响应基因与血管生成相关，包括细胞因子、生长相关因子、粘附蛋白、细胞基质、信号转导、细胞外基质（ECM）和炎症分子。蛋白质-蛋白质相互作用的综合知识显示，12种机械敏感基因编码的蛋白质在血管系统中具有相互作用的伴侣，证实了它们在血管生成的旁分泌调节中的潜在作用。血管生成基因包括基质细胞蛋白质如Cyr 61/CCN 1、CTGF/CCN 2和腱生蛋白C、VEGF和IGF系统的组分、ECM蛋白质如I型胶原蛋白和蛋白聚糖以及基质金属蛋白酶。在膀胱过度扩张的体内模型中，通过实时PCR独立测试的11种机械响应性血管生成基因中的5种由于压力超负荷而上调，包括Cyr 61/CCN 1、CTGF/CCN 2、MCP-1、VEGF-A、MMP-1和中期因子。与此同时，血管生成基因启动子的分子解剖揭示了myc相关锌指蛋白MAZ的GA盒结合的存在，该蛋白通常发现于机械响应转录因子（例如，NF-kappaB），这表明这些因子的协调活性可能会诱导选择性血管生成基因转录。这些数据表明，机械控制的血管生成基因是一个不可分割的一部分，适应性和可塑性的机械过载的反应。
Studies were performed to examine the extent to which mechanical stimuli mediate control of angiogenesis in bladder cells both in vitro and in vivo. Differential gene expression between control nonstretched and cyclically stretched bladder smooth muscle cells was assessed using oligonucleotide microarrays and pathway analysis by the web tool Fast Assignment and Transference of Information (FatiGO). Data showed that a substantial proportion (33 of 86) of mechanically responsive genes were angiogenesis-related and include cytokines, growth-related factors, adhesion proteins, and matricellular, signal transduction, extracellular matrix (ECM), and inflammatory molecules. Integrative knowledge of protein-protein interactions revealed that 12 mechano-sensitive gene-encoded proteins have interacting partner(s) in the vascular system confirming their potential role in paracrine regulation of angiogenesis. Angiogenic genes include matricellular proteins such as Cyr61/CCN1, CTGF/CCN2 and tenascin C, components of the VEGF and IGF systems, ECM proteins such as type I collagen and proteoglycans, and matrix metalloproteinases. In an in vivo model of bladder overdistension, 5 of 11 mechano-responsive angiogenic genes, independently tested by real-time PCR, were upregulated as a result of pressure overload including Cyr61/CCN1, CTGF/CCN2, MCP-1, VEGF-A, MMP-1, and midkine. Meanwhile, the molecular anatomy of angiogenic gene promoters reveals the presence of GA box-binding for the myc-associated zinc finger protein, MAZ, often found adjacent to binding sites for mechano-responsive transcription factors (e.g., NF-kappaB), suggesting that the coordinated activity of these factors may induce selective angiogenic gene transcription. These data suggest that mechanical control of angiogenic genes is an integral part of the adaptive and plasticity responses to mechanical overload.