Progranulin is a mediator of the wound response
Progranulin is a mediator of the wound response
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DOI：
10.1038/nm816
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发表时间：
2003-02-01
期刊：
影响因子：
82.9
通讯作者：
Bateman, A
中科院分区：
文献类型：
--
作者：
He, ZH;Ong, CHP;Bateman, A
在美国，每年有125万人遭受烧伤，650万人经历慢性皮肤溃疡，通常来自糖尿病，压力或静脉淤滞（1）。生长因子是伤口修复的重要介质（1，2），但迄今为止，它们作为伤口治疗的治疗剂的成功有限（1，2）。因此，有必要确定新的伤口反应调节因子，但近年来很少出现（1，2）。颗粒蛋白前体（3）（也称为颗粒蛋白或上皮素前体（4）、顶粒蛋白（5）或PC衍生生长因子（6））是参与肿瘤发生（6-11）和发展（12，13）的生长因子。已经从炎症细胞中分离出来源于颗粒蛋白前体的肽（14），这导致了颗粒蛋白前体基因产物参与创伤反应的建议（10，14），但这仍然未得到证实。我们报告，在小鼠经皮穿刺伤口，颗粒蛋白前体mRNA表达的炎症浸润，并高度诱导真皮成纤维细胞和内皮细胞损伤后。当应用于皮肤伤口时，颗粒蛋白前体增加伤口中中性粒细胞、巨噬细胞、血管和成纤维细胞的积累。它直接作用于分离的真皮成纤维细胞和内皮细胞，以促进分裂、迁移和毛细血管样小管结构的形成。因此，颗粒蛋白前体是一种可能的创伤相关生长因子。
Annually, 1.25 million individuals suffer burns in the United States and 6.5 million experience chronic skin ulcers, often from diabetes, pressure or venous stasis(1). Growth factors are essential mediators of wound repair(1,2), but their success as therapeutics in wound treatment has, so far, been limited(1,2). Therefore, there is a need to identify new wound-response regulatory factors, but few have appeared in recent years(1,2). Progranulin(3) (also called granulin or epithelin precursor(4), acrogranin(5) or PC-derived growth factor(6)) is a growth factor involved in tumorigenesis(6-11) and development(12,13). Peptides derived from progranulin have been isolated from inflammatory cells(14), which led to suggestions that progranulin gene products are involved in the wound response(10,14), but this remains undemonstrated. We report that in murine transcutaneous puncture wounds, progranulin mRNA is expressed in the inflammatory infiltrate and is highly induced in dermal fibroblasts and endothelia following injury. When applied to a cutaneous wound, progranulin increased the accumulation of neutrophils, macrophages, blood vessels and fibroblasts in the wound. It acts directly on isolated dermal fibroblasts and endothelial cells to promote division, migration and the formation of capillary-like tubule structures. Progranulin is, therefore, a probable wound-related growth factor.