IFOM-inStem Joint Research Laboratory, Centre for Inflammation and Tissue Homeostasis, Institute for Stem Cell Science and Regenerative Medicine, Bangalore, India.
Thumbay Research Institute for Precision Medicine, Gulf Medical University, Ajman, UAE.
Exp Dermatol. 2022 Aug;31(8):1188-1201. doi: 10.1111/exd.14573. Epub 2022 Apr 6.
The wound healing process is a product of three successive and overlapping phases of inflammation, proliferation and remodelling. Considerable efforts have been invested in deconstructing the intercellular crosstalk that orchestrates tissue repair, and we investigated the role of neuropeptides released from peripheral neurons upon injury in mediating these interactions. Amongst the most abundant of these neuropeptides secreted by nerves in the skin, is Substance P (SP). Given the role of dermal fibroblasts in coordinating multiple processes in the wound healing program, the effect of SP on human dermal fibroblasts of different ages was evaluated. The use of a substrate that recapitulates the mechanical properties of the in vivo tissue revealed novel effects of SP on dermal fibroblasts, including a block in inflammatory cytokine expression. Moreover, SP can promote expression of some extracellular matrix components and generates signals that regulate angiogenesis. Interestingly, the response of fibroblasts to SP was reduced concomitant with donor age. Altogether, SP acts to inhibit the inflammatory responses and promote proliferation-associated responses in an age-dependent manner in dermal fibroblasts, suggesting a role as a molecular switch between the inflammatory and proliferative phases of the wound healing response.
伤口愈合过程是炎症、增殖和重塑三个连续重叠阶段的产物。人们投入了大量精力来解构协调组织修复的细胞间串扰，我们研究了损伤时外周神经元释放的神经肽在介导这些相互作用中的作用。在皮肤神经分泌的最丰富的神经肽中，有 P 物质 (SP)。鉴于真皮成纤维细胞在协调伤口愈合过程中的多个过程中的作用，评估了 SP 对不同年龄的人真皮成纤维细胞的影响。使用一种能够重现体内组织力学特性的基质，揭示了 SP 对真皮成纤维细胞的新作用，包括阻断炎症细胞因子的表达。此外，SP 可以促进某些细胞外基质成分的表达，并产生调节血管生成的信号。有趣的是，成纤维细胞对 SP 的反应随着供体年龄的增加而降低。总的来说，SP 以一种依赖于年龄的方式作用于真皮成纤维细胞，抑制炎症反应并促进增殖相关反应，提示其在伤口愈合反应的炎症和增殖阶段之间充当分子开关。
