Thrombospondin 1 synthesis and function in wound repair.
Thrombospondin 1 synthesis and function in wound repair.
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发表时间：
1996-06
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通讯作者：
L. DiPietro;N. Nissen;R. Gamelli;A. Koch;J. Pyle;P. Polverini
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作者：
L. DiPietro;N. Nissen;R. Gamelli;A. Koch;J. Pyle;P. Polverini
血小板反应蛋白1（TSP1）是一种多功能的细胞外基质分子，属于同源糖蛋白家族。TSP1可以由参与伤口修复的许多细胞类型产生，包括角质形成细胞、成纤维细胞、内皮细胞和巨噬细胞。为了研究创伤中TSP1合成的动力学，分析了来自鼠全层切除皮肤创伤的mRNA。TSP1 mRNA在正常皮肤中检测不到，但在早期伤口中存在。第1天后，伤口内的TSP1 mRNA水平缓慢下降，恢复到第10天不可检测。原位杂交显示，创伤内TSP1 mRNA的主要来源是炎性浸润中的巨噬细胞样细胞。为了探索损伤部位产生的TSP 1的功能，用反义TSP 1寡聚物处理伤口。反义处理的伤口含有比对照少55%至66%的TSP1阳性巨噬细胞，并表现出明显的修复延迟。这种延迟包括上皮再生率降低以及真皮重组延迟。结果表明，由巨噬细胞产生的TSP1促进修复过程，并提供证据表明TSP1的产生是最佳伤口愈合的重要组成部分。
Thrombospondin 1 (TSP1) is a multifunctional extracellular matrix molecule that belongs to a family of homologous glycoproteins. TSP1 can be produced by many cell types that are involved in wound repair, including keratinocytes, fibroblasts, endothelial cells, and macrophages. To investigate the kinetics of TSP1 synthesis in wounds, mRNA from murine full thickness excisional dermal wounds was analyzed. TSP1 mRNA was undetectable in normal skin but was present in early wounds. After day 1, TSP1 mRNA levels within wounds slowly decreased, returning to undectable day 10. In situ hybridization revealed that the primary source of the TSP1 mRNA within wounds was macrophage-like cells in the inflammatory infiltrate. To explore the function of TSP1 production in sites of injury, wounds were treated with antisense TSP1 oligomers. Antisense-treated wounds contained 55 to 66% less TSP1-positive macrophages than control and exhibited a marked delay in repair. This delay included a decreased rate of re-epithelialization as well as a delay in dermal reorganization. The results suggest that TSP1 production by macrophages facilitates the repair process and provide evidence that TSP1 production is an important component of optimal wound healing.