Role of CD44 in the reaction of vascular smooth muscle cells to arterial wall injury
Role of CD44 in the reaction of vascular smooth muscle cells to arterial wall injury
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DOI：
10.1172/jci118455
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发表时间：
1996-02-01
影响因子：
15.9
通讯作者：
Haber, E
中科院分区：
文献类型：
--
作者：
Jain, M;He, Q;Haber, E
CD 44是透明质酸的主要受体，是一种广泛分布的细胞表面蛋白聚糖，参与细胞活化、增殖和迁移。这些过程也是血管平滑肌细胞对动脉壁损伤的反应的中心。我们评估了CD 44及其亚型CD 44-v6在体外和体内血管平滑肌细胞上的表达，并评估了CD 44在DNA合成中的作用。培养的血管平滑肌细胞表达的CD 44和CD 44-v6的水平等于或高于β（1）和β（3）整合素。在大鼠颈动脉球囊损伤模型中，CD 44和CD 44-v6 mRNA在损伤后血管平滑肌细胞中上调，并且CD 44蛋白表达在生长的新生内膜的管腔边缘最大，表达CD 44的平滑肌细胞增殖活跃，并且透明质酸表达在损伤后以与CD 44类似的时间模式增加。通过与透明质酸结合，CD 44使培养的人和大鼠平滑肌细胞的DNA合成分别增加48+/-7.8%和100+/-12.5%，这一作用可被阻断透明质酸结合的抗CD 44抗体抑制。这些观察结果支持CD 44在血管平滑肌细胞对动脉壁损伤的反应中的作用。
CD44, the principal receptor for hyaluronic acid, is a widely distributed cell surface proteoglycan involved in cellular activation, proliferation, and migration. These processes are also central to the vascular smooth muscle cell's response to arterial wall injury. We evaluated the expression of CD44 and its isoform, CD44-v6, on vascular smooth muscle cells in vitro and in vivo and assessed the role of CD44 in DNA synthesis. Cultured vascular smooth muscle cells expressed CD44 and CD44-v6 at levels equal to or higher than those of the beta(1) and beta(3) integrins. In a rat carotid artery balloon injury model, CD44 and CD44-v6 mRNAs were upregulated in vascular smooth muscle cells after injury, and CD44 protein expression was greatest at the luminal edge of the growing neointima, CD44-expressing smooth muscle cells proliferated actively, and hyaluronic acid expression increased after injury in a temporal pattern similar to that of CD44. Through binding to hyaluronic acid, CD44 augmented DNA synthesis in cultured human and rat smooth muscle cells by 48+/-7.8 and 100+/-12.5%, respectively, an effect inhibited by an anti-CD44 antibody that blocked hyaluronate binding. These observations support a role for CD44 in the reaction of vascular smooth muscle cells to arterial wall injury.