Sawaya Andrew P, Vecin Nicole M, Burgess Jamie L, Ojeh Nkemcho, DiBartolomeo Gabrielle, Stone Rivka C, Pastar Irena, Tomic-Canic Marjana
Wound Healing and Regenerative Medicine Research Program, Dr Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, United States.
Faculty of Medical Sciences, The University of the West Indies, Bridgetown, Barbados.
Front Med (Lausanne). 2023 Aug 24;10:1207538. doi: 10.3389/fmed.2023.1207538. eCollection 2023.
Calreticulin is recognized as a multifunctional protein that serves an essential role in diverse biological processes that include wound healing, modification and folding of proteins, regulation of the secretory pathway, cell motility, cellular metabolism, protein synthesis, regulation of gene expression, cell cycle regulation and apoptosis. Although the role of calreticulin as an endoplasmic reticulum-chaperone protein has been well described, several studies have demonstrated calreticulin to be a highly versatile protein with an essential role during wound healing. These features make it an ideal molecule for treating a complex, multifactorial diseases that require fine tuning, such as chronic wounds. Indeed, topical application of recombinant calreticulin to wounds in multiple models of wound healing has demonstrated remarkable pro-healing effects. Among them include enhanced keratinocyte and fibroblast migration and proliferation, induction of extracellular matrix proteins, recruitment of macrophages along with increased granulation tissue formation, all of which are important functions in promoting wound healing that are deregulated in chronic wounds. Given the high degree of diverse functions and pro-healing effects, application of exogenous calreticulin warrants further investigation as a potential novel therapeutic option for chronic wound patients. Here, we review and highlight the significant effects of topical application of calreticulin on enhancing wound healing and its potential as a novel therapeutic option to shift chronic wounds into healing, acute-like wounds.
钙网蛋白被认为是一种多功能蛋白质，在多种生物过程中发挥着重要作用，包括伤口愈合、蛋白质的修饰与折叠、分泌途径的调节、细胞运动、细胞代谢、蛋白质合成、基因表达调控、细胞周期调控以及细胞凋亡。尽管钙网蛋白作为内质网伴侣蛋白的作用已得到充分描述，但多项研究表明，钙网蛋白是一种高度通用的蛋白质，在伤口愈合过程中起着至关重要的作用。这些特性使其成为治疗复杂的多因素疾病（如慢性伤口）的理想分子，这类疾病需要精细调节。事实上，在多种伤口愈合模型中，将重组钙网蛋白局部应用于伤口已显示出显著的促愈合效果。其中包括增强角质形成细胞和成纤维细胞的迁移与增殖、诱导细胞外基质蛋白、招募巨噬细胞以及增加肉芽组织形成，所有这些都是促进伤口愈合的重要功能，而在慢性伤口中这些功能失调。鉴于其高度多样的功能和促愈合效果，外用钙网蛋白作为慢性伤口患者潜在的新型治疗选择值得进一步研究。在此，我们综述并强调局部应用钙网蛋白对促进伤口愈合的显著作用及其作为将慢性伤口转变为愈合的急性样伤口的新型治疗选择的潜力。
