The matricellular protein thrombospondin-1 globally regulates cardiovascular function and responses to stress via CD47.
The matricellular protein thrombospondin-1 globally regulates cardiovascular function and responses to stress via CD47.
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DOI：
10.1016/j.matbio.2012.01.005
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发表时间：
2012-04
期刊：
影响因子：
6.9
通讯作者：
Isenberg, Jeffrey S.
中科院分区：
文献类型：
--
作者：
Roberts, David D.;Miller, Thomas W.;Rogers, Natasha M.;Yao, Mingyi;Isenberg, Jeffrey S.
基质细胞蛋白通过与特定的细胞表面受体结合并与细胞外基质蛋白、分泌酶和生长因子相互作用，在调节细胞行为中发挥多种作用。对涉及血小板反应蛋白-1的这种相互作用的研究已经揭示了在损伤反应和癌症的发病机制中的几种生理功能和作用，但是缺乏血小板反应蛋白-1的小鼠的相对温和的表型表明血小板反应蛋白-1不会是可以在治疗上利用的核心参与者。然而，最近的研究集中在通过其受体CD 47的信号传导上，已经发现了血小板反应蛋白-1在心血管动力学、止血、免疫和线粒体稳态的急性调节中的更关键的作用。这些功能中的几个是通过对经典一氧化氮途径的有效和冗余抑制来介导的。相反，在主要的慢性衰老疾病中，组织血小板反应蛋白-1水平升高可能是这些疾病的特征性一氧化氮信号传导不足的原因，靶向CD 47的实验疗法显示出治疗这些慢性疾病以及与血小板反应蛋白-1表达升高相关的急性应激状况的希望。
Matricellular proteins play diverse roles in modulating cell behavior by engaging specific cell surface receptors and interacting with extracellular matrix proteins, secreted enzymes, and growth factors. Studies of such interactions involving thrombospondin-1 have revealed several physiological functions and roles in the pathogenesis of injury responses and cancer, but the relatively mild phenotypes of mice lacking thrombospondin-1 suggested that thrombospondin-1 would not be a central player that could be exploited therapeutically. Recent research focusing on signaling through its receptor CD47, however, has uncovered more critical roles for thrombospondin-1 in acute regulation of cardiovascular dynamics, hemostasis, immunity, and mitochondrial homeostasis. Several of these functions are mediated by potent and redundant inhibition of the canonical nitric oxide pathway. Conversely, elevated tissue thrombospondin-1 levels in major chronic diseases of aging may account for the deficient nitric oxide signaling that characterizes these diseases, and experimental therapeutics targeting CD47 show promise for treating such chronic diseases as well as acute stress conditions that are associated with elevated thrombospondin-1 expression.
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影响因子：
7.3
作者：
Gélinas, DS;Bernatchez, PN;Sirois, MG
通讯作者：
Sirois, MG
DOI：
10.1073/pnas.74.8.3203
发表时间：
1977-01-01
影响因子：
11.1
作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Frazier, William A.
影响因子：
7.8
作者：
BORNSTEIN, P
通讯作者：
BORNSTEIN, P