Faculty of Health Sciences, Plastic Surgery Department, University of the Witwatersrand, Johannnesburg, South Africa and Adar science Inc., Irvine, CA, USA.
Int Wound J. 2013 Apr;10(2):185-92. doi: 10.1111/j.1742-481X.2012.00967.x. Epub 2012 Apr 11.
As with all physiologic processes, chronic wounds are associated with unique intracellular and cellular/extracellular matrix (ECM) receptor types and signalling messages. These cellular receptors mediate responses of the epidermis to provisional wound matrix and change in form and number in cases of impaired wound healing. Integrins are the major cell-surface receptors for cell adhesion and migration and epidermal keratinocytes express several integrins that bind ECM ligands in provisional wound ECM. Integrin receptors and more particularly integrin clusters and focal adhesion points appear to influence epidermal and dermal cell matrix interactions, cell motility, cell phenotype and ultimate healing trajectory. In chronic wounds, a variety of changes in receptors have been identified: decreased integrin α5β1 receptors affect the integration of fibronectin and subsequent keratinocyte migration; integrin αvβ6 stimulate transforming growth factor (TGF)-β and may increase the susceptibility to ulceration and fibrosis; however, TGF-β signal receptors have been found to be dysfunctional in many chronic wounds; additionally receptor interactions result in increased senescent cells including fibroblasts, myofibroblasts and even keratinocytes - this produces a degradative ECM and wound bed and corrosive chronic wound fluid. The activation or inhibition of integrin receptors by various agents may provide an excellent means of influencing wound healing. This process offers an earlier intervention into the wound healing cascade promoting intrinsic healing and elaboration of growth factors and ECM proteins, which may be more cost effective than the traditional attempts at extrinsic addition of these agents.
与所有生理过程一样，慢性伤口与独特的细胞内和细胞/细胞外基质 (ECM) 受体类型和信号消息相关。这些细胞受体介导表皮对临时伤口基质的反应，并在伤口愈合受损的情况下改变形态和数量。整合素是细胞黏附和迁移的主要细胞表面受体，表皮角质形成细胞表达几种整合素，这些整合素结合临时伤口 ECM 中的 ECM 配体。整合素受体，特别是整合素簇和黏着斑点，似乎会影响表皮和真皮细胞基质相互作用、细胞迁移、细胞表型和最终愈合轨迹。在慢性伤口中，已经确定了多种受体变化：整合素 α5β1 受体减少会影响纤维连接蛋白的整合和随后的角质形成细胞迁移；整合素 αvβ6 刺激转化生长因子 (TGF)-β，可能增加溃疡和纤维化的易感性；然而，许多慢性伤口中发现 TGF-β 信号受体功能失调；此外，受体相互作用导致包括成纤维细胞、肌成纤维细胞甚至角质形成细胞在内的衰老细胞增加——这会产生降解的 ECM 和伤口床以及腐蚀性的慢性伤口液。各种试剂对整合素受体的激活或抑制可能提供一种极好的影响伤口愈合的方法。这个过程提供了对伤口愈合级联的早期干预，促进内在愈合和生长因子和 ECM 蛋白的产生，这可能比传统的外源添加这些物质更具成本效益。
