Neurotrophin and neurotrophin receptors in vascular smooth muscle cells. Regulation of expression in response to injury.
Neurotrophin and neurotrophin receptors in vascular smooth muscle cells. Regulation of expression in response to injury.
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发表时间：
1995
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通讯作者：
Michael J. O'Donovan;R. Miranda;R. Kraemer;T. McCaffrey;L. Tessarollo;D. Mahadeo;S. K. Sharif;D. M
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作者：
Michael J. O'Donovan;R. Miranda;R. Kraemer;T. McCaffrey;L. Tessarollo;D. Mahadeo;S. K. Sharif;D. M
神经营养因子是一个相关的多肽生长因子家族，包括神经生长因子（NGF）、脑源性神经营养因子（BDNF）和神经营养因子（NT）-3和NT-4/5，它们促进不同胚胎神经元的存活和分化。在这里，我们定义了一个新的功能作用的神经营养因子，作为自分泌或局部旁分泌介质的血管平滑肌细胞迁移。我们已经确定了神经营养素，和他们的同源受体，酪氨酸激酶，在人类和大鼠血管平滑肌细胞在体内。在体外，培养的人平滑肌细胞表达BDNF、NT-3和trk A、B和C。同样，大鼠平滑肌细胞表达所有三种trk受体以及所有四种神经营养因子。此外，NGF在亚纳摩尔浓度下诱导培养的人平滑肌细胞迁移。在大鼠主动脉球囊去内皮化血管损伤模型中，NGF、BNDF及其受体trk A和trk B的表达在3天内在损伤区域显著增加，并在新生内膜形成期间持续存在。在人冠状动脉粥样硬化病变中，BDNF、NT-3和NT-4/5以及trk B和trk C受体可在平滑肌细胞中被证实。这些结果表明，神经营养因子在调节血管平滑肌细胞对损伤的反应中起重要作用。
The neurotrophins, a family of related polypeptide growth factors including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3 and NT-4/5 promote the survival and differentiation of distinctive sets of embryonic neurons. Here we define a new functional role for neurotrophins, as autocrine or local paracrine mediators of vascular smooth muscle cell migration. We have identified neurotrophins, and their cognate receptors, the trk tyrosine kinases, in human and rat vascular smooth muscle cells in vivo. In vitro, cultured human smooth muscle cells express BDNF; NT-3; and trk A, B, and C. Similarly, rat smooth muscle cells expressed all three trk receptors as well as all four neurotrophins. Moreover, NGF induces cultured human smooth muscle cell migration at subnanomolar concentrations. In the rat aortic balloon deendothelialization model of vascular injury, the expression of NGF, BNDF, and their receptors trk A and trk B increased dramatically in the area of injury within 3 days and persisted during the formation of the neointima. In human coronary atherosclerotic lesions, BDNF, NT-3, and NT-4/5, and the trk B and trk C receptors could be demonstrated in smooth muscle cells. These findings suggest that neurotrophins play an important role in regulating the response of vascular smooth muscle cells to injury.