The lack of thrombospondin-1 (TSP1) dictates the course of wound healing in double-TSP1/TSP2-null mice
The lack of thrombospondin-1 (TSP1) dictates the course of wound healing in double-TSP1/TSP2-null mice
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DOI：
10.1016/s0002-9440(10)64243-5
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发表时间：
2002-09-01
影响因子：
6
通讯作者：
Bornstein, P
中科院分区：
文献类型：
--
作者：
Agah, A;Kyriakides, TR;Bornstein, P
血小板反应蛋白（TSP）1和2具有相同的整体结构，并与许多相同的细胞表面受体相互作用。为了更清楚地阐明它们的生物学作用，我们产生了双TSP 1/TSP 2缺失动物，并将它们的表型与TSP 1和TSP 2缺失小鼠的表型进行了比较。双无效小鼠表现出明显的表型，主要代表在单无效小鼠中观察到的异常的总和。然而，令人惊讶的是，双无效小鼠的伤口愈合反应与TSP 1无效动物相似，而与TSP 2无效小鼠不同。因此，尽管TSP 2缺失小鼠的切除伤口的特征在于增加的新血管形成和加速愈合，但TSP 1缺失和双缺失动物表现出延迟愈合，如炎症的延长持续性和延迟结痂损失所示。免疫组织化学分析显示，与TSP 1基因敲除小鼠相似，双敲除小鼠的肉芽组织没有过度血管化。此外，如在TSP 1-null中，巨噬细胞募集和单核细胞趋化蛋白-1水平的降低表明双null小鼠中伤口愈合反应的炎症阶段受损。我们的数据表明，缺乏TSP 1的结果在双缺陷小鼠的反应中占主导地位，并决定了伤口愈合的过程。这些结果反映了不同的时间和空间表达的TSP 1和TSP 2的愈合伤口。
Thrombospondin (TSP) 1 and 2, share the same overall structure and interact with a number of the same cell-surface receptors. In an attempt to elucidate their biological roles more clearly, we generated double-TSP1/TSP2-null animals and compared their phenotype to those of TSP1- and TSP2-null mice. Double-null mice exhibited an apparent phenotype that primarily represented the sum of the abnormalities observed in the single-null mice. However, surprisingly, the wound-healing response in double-null mice resembled that in TSP1-null animals and differed from that in TSP2-nulls. Thus, although the excisional wounds of TSP2-null mice are characterized by increased neovascularization and heal at an accelerated rate, TSP1-null and double-null animals demonstrated delayed healing, as indicated by the prolonged persistence of inflammation and delayed scab loss. Immunohistochemical analysis showed that, similar to TSP1-null mice, the granulation tissue of double-null mice was not excessively vascularized. Furthermore as in TSP1-nulls, decreases in macrophage recruitment and in the levels of monocyte chemoattractant protein-1 indicated that the inflammatory phase of the wound-healing response was impaired in double-null mice. our data demonstrate that the consequences of a lack of TSP1 predominate in the response of double-null mice, and dictate the course of wound healing. These findings reflect distinct temporal and spatial expressions of TSP1 and TSP2 in the healing wound.