Department of Surgery, International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada.
Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Exp Dermatol. 2022 Apr;31(4):475-484. doi: 10.1111/exd.14516. Epub 2021 Dec 30.
Tissue repair is a very complex event and involves a continuously orchestrated sequence of signals and responses from platelets, fibroblasts, epithelial, endothelial and immune cells. The details of interaction between these signals, which are mainly growth factors and cytokines, have been widely discussed. However, it is still not clear how activated cells at wound sites lessen their activities after epithelialization is completed. Termination of the wound healing process requires a fine balance between extracellular matrix (ECM) deposition and degradation. Maintaining this balance requires highly accurate epithelial-mesenchymal communication and correct information exchange between keratinocytes and fibroblasts. As it has been reported in the literature, a disruption in epithelialization during the process of wound healing increases the frequency of developing chronic wounds or fibrotic conditions, as seen in a variety of clinical cases. Conversely, the potential stop signal for wound healing should have a regulatory role on both ECM synthesis and degradation to reach a successful wound healing outcome. This review briefly describes the potential roles of growth factors and cytokines in controlling the early phase of wound healing and predominantly explores the role of releasable factors from epithelial-mesenchymal interaction in controlling during and the late stage of the healing process. Emphasis will be given on the crosstalk between keratinocytes and fibroblasts in ECM modulation and the healing outcome following a brief discussion of the wound healing initiation mechanism. In particular, we will review the termination of acute dermal wound healing, which frequently leads to the development of hypertrophic scarring.
组织修复是一个非常复杂的事件，涉及血小板、成纤维细胞、上皮细胞、内皮细胞和免疫细胞从血小板、成纤维细胞、上皮细胞、内皮细胞和免疫细胞不断协调的信号和反应序列。这些信号（主要是生长因子和细胞因子）之间的相互作用的细节已经被广泛讨论。然而，仍然不清楚激活的细胞在伤口部位如何在上皮化完成后减少它们的活动。伤口愈合过程的终止需要细胞外基质（ECM）沉积和降解之间的精细平衡。维持这种平衡需要上皮-间充质通讯的高度精确性和角质形成细胞和成纤维细胞之间的正确信息交换。正如文献中报道的那样，在伤口愈合过程中上皮化的中断会增加形成慢性伤口或纤维化的频率，这在各种临床病例中都可以看到。相反，伤口愈合的潜在停止信号应该对 ECM 的合成和降解都有调节作用，以达到成功的伤口愈合结果。本综述简要描述了生长因子和细胞因子在控制伤口愈合早期阶段的潜在作用，主要探讨了上皮-间充质相互作用中释放因子在控制愈合过程中和晚期的作用。重点将放在角质形成细胞和成纤维细胞之间的 ECM 调节和愈合结果上，并在简要讨论伤口愈合起始机制后。特别是，我们将回顾急性皮肤伤口愈合的终止，这通常会导致肥厚性瘢痕的形成。
