Fibroblast invasive migration into fibronectin/fibrin gels requires a previously uncharacterized dermatan sulfate-CD44 proteoglycan
Fibroblast invasive migration into fibronectin/fibrin gels requires a previously uncharacterized dermatan sulfate-CD44 proteoglycan
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DOI：
10.1046/j.0022-202x.2004.22205.x
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发表时间：
2004-02-01
影响因子：
6.5
通讯作者：
Couchman, JR
中科院分区：
文献类型：
--
作者：
Clark, RAF;Lin, FB;Couchman, JR
组织损伤后，成纤维细胞从伤口周围胶原基质迁移到充满纤维蛋白的伤口中对于肉芽组织形成和随后的愈合至关重要。最近，我们发现成纤维细胞从胶原基质迁移到纤维蛋白基质需要纤连蛋白的存在。几个整合素-α 4 β 1，α 5 β 1，和α v β 3-与已知的纤连蛋白结合亲和力是必要的这种侵入性迁移。在这里，我们研究了另一个家庭的细胞表面受体：蛋白聚糖。我们发现成纤维细胞迁移到纤连蛋白/纤维蛋白凝胶中需要硫酸皮肤素。这一结论是基于β-木糖苷对聚糖化和特异性糖胺聚糖降解的抑制。已知结合透明质酸的细胞表面受体CD 44经常作为蛋白聚糖存在，其被各种糖胺聚糖链修饰，包括硫酸乙酰肝素和硫酸软骨素，并且因此可以结合纤连蛋白。我们发现，CD 44 H，非剪接亚型的CD 44，是必要的成纤维细胞侵入纤连蛋白/纤维蛋白凝胶。静息成纤维细胞主要表达非糖基化的CD 44 H核心蛋白，其在与血小板衍生生长因子孵育24小时后与硫酸软骨素和硫酸皮肤素而不是硫酸乙酰肝素一起糖基化，所述血小板衍生生长因子是用于迁移测定的刺激物。这些结果表明，硫酸皮肤素-CD 44 H蛋白聚糖是必不可少的成纤维细胞迁移到纤维蛋白凝块和血小板衍生的生长因子，迁移的刺激，诱导硫酸软骨素和硫酸皮肤素-聚糖化的CD 44 H的生产。
After tissue injury, fibroblast migration from the peri-wound collagenous stroma into the fibrin-laden wound is critical for granulation tissue formation and subsequent healing. Recently we found that fibroblast transmigration from a collagen matrix into a fibrin matrix required the presence of fibronectin. Several integrins-alpha4beta1, alpha5beta1, and alphavbeta3-with known fibronectin binding affinity were necessary for this invasive migration. Here we examined another family of cell surface receptors: the proteoglycans. We found that dermatan sulfate was required for fibroblast migration into a fibronectin/fibrin gel. This conclusion was based on beta-xyloside inhibition of glycanation and specific glycosaminoglycan degradation. CD44, a cell surface receptor known to bind hyaluronan, not infrequently exists as a proteoglycan, decorated with various glycosaminoglycan chains including heparan sulfate and chondroitin sulfate, and as such can bind fibronectin. We found that CD44H, the non-spliced isoform of CD44, was necessary for fibroblast invasion into fibronectin/fibrin gels. Resting fibroblasts expressed mostly nonglycanated CD44H core protein, which became glycanated with chondroitin sulfate and dermatan sulfate, but not heparan sulfate, after a 24 h incubation with platelet-derived growth factor, the stimulus used in the migration assay. These results demonstrate that dermatan sulfate-CD44H proteoglycan is essential for fibroblast migration into fibrin clots and that platelet-derived growth factor, the stimulus for migration, induces the production of chondroitin-sulfate- and dermatan-sulfate-glycanated CD44H.