Endogenous thrombospondin-1 is not necessary for proliferation but is pen-nissive for vascular smooth muscle cell responses to platelet-derived growth factor
Endogenous thrombospondin-1 is not necessary for proliferation but is pen-nissive for vascular smooth muscle cell responses to platelet-derived growth factor
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DOI：
10.1016/j.matbio.2005.01.002
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发表时间：
2005-04-01
期刊：
影响因子：
6.9
通讯作者：
Roberts, DD
中科院分区：
文献类型：
--
作者：
Isenberg, JS;Calzada, MJ;Roberts, DD
我们重新研究了内源性血小板反应蛋白-1（TSP 1）在血管平滑肌细胞（SMC）生长和运动中的作用。基于从TSP 1缺失小鼠中分离并在不存在外源性TSP 1的情况下生长的树突状细胞衍生的SMC以与来自野生型小鼠的等效细胞相当的速率生长并达到略高的密度的能力，TSP 1对于它们的生长不是必需的。低浓度的外源性TSP 1刺激TSP 1无效SMC的生长，但较高剂量的TSP 1或其C-末端结构域是抑制性的。然而，TSP 1基因敲除小鼠的SMC在对血小板源性生长因子的趋化和增殖反应以及在三维培养物中的生长方面存在选择性缺陷。TSP 1的N-和C-末端结构域的重组部分通过不同的整合素受体刺激SMC趋化性。基于这些数据，TSP 1缺失小鼠肌肉组织离体血管生成反应期间SMC生长的相对不足可能是由于血小板衍生生长因子依赖性SMC迁移和/或增殖的限制。© 2005 Elsevier B.V./国际矩阵生物学学会。All rights reserved.
We have reexamined the role of endogenous thrombospondin-1 (TSP1) in growth and motility of vascular smooth muscle cells (SMCs). Based on the ability of aortic-derived SMCs isolated from TSP1 null mice and grown in the absence of exogenous TSP1 to grow at comparable rates and to a slightly higher density than equivalent cells from wild-type mice, TSP1 is not necessary for their growth. Low concentrations of exogenous TSP1 stimulate growth of TSP1 null SMCs, but higher doses of TSP1 or its C-terminal domain are inhibitory. However, SMCs from TSP1 null mice are selectively deficient in chemotactic and proliferative responses to platelet-derived growth factor and in outgrowth in three-dimensional cultures. Recombinant portions of the N- and C-terminal domains of TSP1 stimulate SMC chemotaxis through different integrin receptors. Based on these data, the relative deficiency in SMC outgrowth during an ex vivo angiogenic response of muscle tissue from TSP1 null mice is probably due to restriction of platelet-derived growth factor dependent SMC migration and/or proliferation. © 2005 Elsevier B.V./International Society of Matrix Biology. All rights reserved.