Fibronectin provides a conduit for fibroblast transmigration from collagenous stroma into fibrin clot provisional matrix.
Fibronectin provides a conduit for fibroblast transmigration from collagenous stroma into fibrin clot provisional matrix.
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发表时间：
1997-04
影响因子：
4
通讯作者：
Doris Greiling;Richard A. F. Clark
中科院分区：
文献类型：
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作者：
Doris Greiling;Richard A. F. Clark
损伤后，伤口间隙被含有由血小板和单核细胞释放的生长因子的纤维蛋白/纤维连接蛋白凝块填充。作为对这些因素的反应，成纤维细胞迁移到纤维蛋白凝块中，有助于肉芽组织的形成。成纤维细胞离开正常结缔组织的胶原基质并侵入纤维蛋白凝块的临时基质的作用机制尚未完全确定。为了研究这些机制，我们建立了一个新的体外模型，模拟伤口早期愈合的特定方面，即成纤维细胞从三维胶原基质迁移到纤维蛋白凝块中。这种迁移可由生理浓度的血小板释放物或血小板衍生生长因子BB(PDGF-BB)以浓度依赖的方式诱导。在24小时内，照射后的成纤维细胞几乎和未照射的细胞一样侵入纤维蛋白凝胶，表明迁移与增殖无关。纤溶酶原及其激活剂似乎对纤维蛋白凝块的侵袭是必需的，因为蛋白酶抑制剂减少了迁移量。然而，这些丝氨酸蛋白酶并不是从胶原胶中退出所必需的，因为即使在抑制剂的存在下，成纤维细胞也会从胶原胶中迁移到覆盖着纤维原纤维的表面。从胶原凝胶或纤维蛋白凝胶中去除纤维连接蛋白(FN)显著减少了迁移细胞的数量，这表明FN为迁移提供了一条管道。在体外模型中，RGD多肽和抗α5β1和αvβ3整合素受体亚单位的单抗可抑制细胞运动。因此，成纤维细胞从富含胶原的基质向富含纤维蛋白的基质迁移的功能要求，例如在伤口愈合早期发生的，已经通过这一重要生物过程的体外范例得到了部分定义。
After injury, the wound space is filled with a fibrin/fibronectin clot containing growth factors released by platelets and monocytes. In response to these factors, fibroblasts migrate into the fibrin clot and contribute to the formation of granulation tissue. The functional mechanisms allowing fibroblasts to leave the collagenous matrix of normal connective tissue and invade the provisional matrix of the fibrin clot have not been fully defined. To investigate these mechanisms we established a new in vitro model which simulates specific aspects of early wound healing, that is, the migration of fibroblasts from a three-dimensional collagen matrix into a fibrin clot. This transmigration could be induced by physiological concentrations of platelet releasate or platelet-derived growth factor BB (PDGF-BB) in a concentration-dependent manner. At 24 hours irradiated fibroblasts invaded the fibrin gel almost as well as non-irradiated cells, indicating that transmigration was independent of proliferation. Plasminogen and its activators appear to be necessary for invasion of the fibrin clot since protease inhibitors decreased the amount of migration. These serine proteases, however, were not necessary for exit from the collagen gel as fibroblasts migrated out of the collagen gel onto a surface coated with fibrin fibrils even in the presence of inhibitors. Removal of fibronectin (FN) from either the collagen gel or the fibrin gel markedly decreased the number of migrating cells, suggesting that FN provides a conduit for transmigration. Cell movement in the in vitro model was inhibited by RGD peptide, and by monoclonal antibodies against the subunits of the alpha5 beta1 and alpha v beta3 integrin receptor. Thus, the functional requirements for fibroblast transmigration from collagen-rich to fibrin-rich matrices, such as occurs in early wound healing, have been partially defined using an in vitro paradigm of this important biologic process.