Overview of the role for calreticulin in the enhancement of wound healing through multiple biological effects
Overview of the role for calreticulin in the enhancement of wound healing through multiple biological effects
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DOI：
10.1038/sj.jidsymp.5650011
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发表时间：
2006-09-01
影响因子：
--
通讯作者：
Cadacio, Caprice L.
中科院分区：
文献类型：
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作者：
Gold, Leslie I.;Rahman, Mohammad;Cadacio, Caprice L.
钙网蛋白（CRT）是一种细胞内的伴侣蛋白，对蛋白质在内质网中的正常折叠和运输至关重要，最近被认为是细胞外功能的关键调节剂，特别是在介导细胞迁移和凋亡细胞吞噬方面。与这些功能一致，我们表明，局部应用CRT通过引起小鼠和猪正常和受损皮肤损伤动物模型中上皮迁移和肉芽组织形成的剂量依赖性增加，对伤口愈合过程产生深远影响。CRT的这些作用在体外得到证实，我们使用伤口/划痕板试验表明，CRT强烈诱导人角质形成细胞和成纤维细胞的细胞迁移/伤口闭合，并刺激人角质形成细胞、成纤维细胞和血管内皮细胞的细胞增殖，为CRT在修复中的作用提供了机制见解。同样，在两种动物模型中，伤口的组织学显示基底角化细胞和真皮成纤维细胞明显增殖，真皮细胞致密，巨噬细胞数量明显增加，胶原纤维沉积组织良好。因此，CRT通过招募修复必需的细胞进入伤口，刺激细胞生长和增加细胞外基质的产生，深刻地影响伤口愈合过程。
Calreticulin (CRT), an intracellular chaperone protein crucial for the proper folding and transport of proteins through the endoplasmic reticulum, has more recent acclaim as a critical regulator of extracellular functions, particularly in mediating cellular migration and as a requirement for phagocytosis of apoptotic cells. Consistent with these functions, we show that the topical application of CRT has profound effects on the process of wound healing by causing a dose-dependent increase in epithelial migration and granulation tissue formation in both murine and porcine normal and impaired animal models of skin injury. These effects of CRT are substantiated, in vitro, as we show that CRT strongly induces cell migration/wound closure of human keratinocytes and fibroblasts, using a wound/scratch plate assay, and stimulates cellular proliferation of human keratinocytes, fibroblasts, and vascular endothelial cells, providing mechanistic insight into how CRT functions in repair. Similarly, in both animal models, the histology of the wounds show marked proliferation of basal keratinocytes and dermal fibroblasts, dense cellularity of the dermis with notably increased numbers of macrophages and well-organized collagen fibril deposition. Thus, CRT profoundly affects the wound healing process by recruiting cells essential for repair into the wound, stimulating cell growth, and increasing extracellular matrix production.