Tannenbaum J E, Waleh N S, Mauray F, Breuss J, Pytela R, Kramer R H, Clyman R I
Cardiovascular Research Institute, University of California, San Francisco 94143-0544, USA.
Pediatr Res. 1995 May;37(5):561-70. doi: 10.1203/00006450-199505000-00001.
Anatomical closure of the ductus arteriosus (DA) requires normally quiescent smooth muscle cells (SMC) to migrate out of the muscle media into the subendothelial space, forming intimal mounds that eventually coalesce to occlude the vessel's lumen. Transforming growth factor-beta 1 (TGF beta 1), a potent modulator of vascular SMC migration, is found in the wall of the closing DA. We examined the effect of TGF beta 1 on the migration of fetal lamb DA-SMC. Although TGF beta 1 has been shown to be a chemoattractant for other mesenchymal cells, it had no chemotactic effect on DA-SMC; furthermore, TGF beta 1 did not enhance the migration of DA-SMC (as has been reported for aortic SMC). Rather, incubating DA-SMC with TGF beta 1 for 22 h decreased the rate of migration of SMC on extracellular matrix substrata composed of fibronectin, vitronectin, laminin, and collagen I and IV. Exposure of DA-SMC to TGF beta 1 was associated with an increase in the formation of focal adhesion plaques (tight associations between the cells' surface and extracellular matrix). DA-SMC use integrin receptors to attach to and migrate on extracellular matrix components. The decrease in DA-SMC migration was not associated with a significant change in the profile of integrin receptors expressed by the cell. TGF beta 1 had little effect on overall DA-SMC integrin expression, except for a modest increase in the fibronectin receptor (alpha 5 beta 1 integrin). Rather, the decrease in migration and changes in cell morphology were associated with an increased ability of integrin receptors to associate with the cytoskeleton. TGF beta 1 appears to anchor the cell's cytoskeleton to the extracellular matrix, making the cells more adherent and less capable of migrating.
动脉导管（DA）的解剖学闭合需要通常处于静止状态的平滑肌细胞（SMC）从肌层迁移至内皮下间隙，形成内膜丘，最终融合以闭塞血管腔。转化生长因子-β1（TGF-β1）是血管SMC迁移的强效调节剂，在闭合中的DA壁中可检测到。我们研究了TGF-β1对胎羊DA-SMC迁移的影响。尽管TGF-β1已被证明对其他间充质细胞具有趋化作用，但它对DA-SMC没有趋化作用；此外，TGF-β1并未增强DA-SMC的迁移（如对主动脉SMC的报道）。相反，将DA-SMC与TGF-β1孵育22小时会降低SMC在由纤连蛋白、玻连蛋白、层粘连蛋白以及I型和IV型胶原组成的细胞外基质底物上的迁移速率。DA-SMC暴露于TGF-β1与粘着斑（细胞表面与细胞外基质之间的紧密连接）形成增加有关。DA-SMC利用整合素受体附着于细胞外基质成分并在其上迁移。DA-SMC迁移的减少与细胞表达的整合素受体谱的显著变化无关。TGF-β1对DA-SMC整体整合素表达影响很小，除了纤连蛋白受体（α5β1整合素）有适度增加。相反，迁移的减少和细胞形态的变化与整合素受体与细胞骨架结合能力的增强有关。TGF-β1似乎将细胞骨架锚定到细胞外基质，使细胞更具粘附性且迁移能力降低。
