Matricellular homologs in the foreign body response - Hevin suppresses inflammation, but Hevin and SPARC together diminish angiogenesis
Matricellular homologs in the foreign body response - Hevin suppresses inflammation, but Hevin and SPARC together diminish angiogenesis
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DOI：
10.1016/s0002-9440(10)62312-7
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发表时间：
2005-03-01
影响因子：
6
通讯作者：
Sage, EH
中科院分区：
文献类型：
--
作者：
Barker, TH;Framson, P;Sage, EH
植入的异物用于恢复或辅助组织功能，引起初始急性炎症反应，随后是慢性纤维化，导致生物材料截留在厚的、血管化不良的胶原囊中。基质细胞蛋白，分泌的大分子，与细胞外基质蛋白相互作用，但本身不提供结构作用，已被确定为重要的介质的异物反应，包括炎症，血管生成，胶原蛋白的合成和组装。在这份报告中，我们描绘的hevin和hevin，两个同源的hevin家族的基质细胞蛋白质，在异物反应的功能。尽管它们的序列相似，hevin和hevin介导不同方面的纤维化反应。使用靶向基因缺失的小鼠，我们发现hevin是生物材料诱导的炎症进展的核心，而hevin调节胶原囊的形成。虽然在没有任何一种蛋白质的情况下，胶囊内的血管密度不变，但SPARC-hevin双无效胶囊显示血管数量大幅增加，表明这两种蛋白质在抑制血管生成中的代偿功能。这些结果为种植体技术的进一步发展提供了重要信息。
Implanted foreign materials, used to restore or assist tissue function, elicit an initial acute inflammatory response followed by chronic fibrosis that leads to the entrapment of the biomaterial in a thick, poorly vascularized collagenous capsule. Matricellular proteins, secreted macromolecules that interact with extracellular matrix proteins but do not in themselves serve structural roles, have been identified as important mediators of the foreign body response that includes inflammation, angiogenesis, and collagen synthesis and assembly. In this report we delineate functions of hevin and SPARC, two homologs of the SPARC family of matricellular proteins, in the foreign body response. Despite their sequence similarity, hevin and SPARC mediate different aspects of this fibrotic response. Using mice with targeted gene deletions, we show that hevin is central to the progression of biomaterial-induced inflammation whereas SPARC regulates the formation of the collagenous capsule. Although vascular density within the capsule is unaltered in the absence of either protein, SPARC-hevin double-null capsules show substantially increased numbers of vessels, indicating compensatory functions for these two proteins in the inhibition of angiogenesis. These results provide important information for further development of implant technology.