Fibroblast remodelling of the dermis during rejuvenation and scarring events

面部的皮肤是独特的，有证据表明具有出色的伤口愈合性能(如较少的疤痕形成)，但对某些皮肤状况的敏感性较高，包括痤疮和瘢痕疙瘩。此外，疤痕形成因种族而异，黑人和东亚人的皮肤尤其容易形成疤痕。真皮细胞外基质(ECM)决定了皮肤的物理特征(如疤痕僵硬)，是美容激光疗法显著改善结构的部位。ECM主要是真皮成纤维细胞的产物，真皮成纤维细胞是局部和身体不同部位的异质细胞。面部真皮独特地起源于神经脊(NC)，而身体真皮则由中胚层组织发育而来。我们认为，NC来源的真皮成纤维细胞具有促进伤口愈合的特殊功能，但当调控不当时，会导致病理性瘢痕。我们发现，在伤口修复过程中，不同解剖部位的组织学和转录水平存在显著差异。此外，我们对瘢痕疙瘩(40%发生在面部)的研究显示，NC标记(例如GD2)大量表达，以及反映NC细胞错误分化的软骨样ECM[7]。重要的是，瘢痕疙瘩来自非洲-加勒比黑人皮肤，尽管种族如何影响真皮ECM尚不清楚。需要从机理上了解局部皮肤的差异；健康面部皮肤的特殊愈合特性可以帮助改善伤口结果和基于ECM的年轻化技术。此外，种族皮肤在伤口愈合方面的比较可能有助于揭开为什么会存在差异。这个项目将揭示真皮重塑的解剖变异，并对高加索人和非洲加勒比人的皮肤进行比较。我们的目标是确定可用于改善伤口愈合结果的途径和分子，包括用于皮肤恢复活力的应用。

The skin of the face is distinctive, with evidence for superior wound healing properties (e.g. less scarring), yet heightened susceptibility to certain skin conditions, including acne and keloid scars In addition, scarring varies between ethnicities, with black and east Asian skin particularly susceptible The dermal extracellular matrix (ECM) dictates the physical features of the skin (e.g. scar stiffness) and is the site of significant structural improvements offered by cosmetic laser treatments The ECM is largely the product of dermal fibroblasts, which are heterogeneous, locally and between body sites. The facial dermis is uniquely derived from the neural crest (NC), whereas the body dermis develops from mesoderm tissue. e propose NC-derived dermal fibroblasts have special features that promote wound healing, but when mis-regulated drive pathological scarring.We have discovered significant histological and transcriptional variations between anatomical sites during wound repair. Also, our studies of keloids (>40% develop on the face) revealed abundant expression of NC markers (e.g. GD2), and a cartilage-like ECM that reflects mis-differentiation of NC cells [7]. Importantly, the keloids were from black Afro-Caribbean skin, although how ethnicity affects dermal ECM is unknown.A mechanistic understanding of the regional skin differences is needed; the special healing properties of healthy facial skin could help improve wound outcomes and ECM-based rejuvenation techniques. In addition, comparisons between ethnic skins in wound healing might help unravel why differences exist. This project will uncover anatomical variation in dermal remodelling, and compare Caucasian and Afro-Caribbean skin. We aim to identify pathways and molecules that may be harnessed to improve wound healing outcomes, including for skin rejuvenation applications.