Fibroblast remodelling of the dermis during rejuvenation and scarring events

面部皮肤特征明显，有证据表明其具有上级伤口愈合特性（例如，较少的疤痕），但对某些皮肤状况（包括痤疮和瘢痕疙瘩疤痕）的易感性增加。此外，疤痕在种族之间变化，皮肤细胞外基质（ECM）决定了皮肤的物理特征，ECM主要是真皮成纤维细胞的产物，其在局部和身体部位之间是异质的。面部真皮是唯一来源于神经嵴（NC），而身体真皮发展中胚层组织。我们提出NC衍生的真皮成纤维细胞具有促进伤口愈合的特殊功能，但当错误调节时会导致病理性瘢痕形成。此外，我们对瘢痕疙瘩（>40%发生在面部）的研究揭示了NC标志物（例如GD 2）的丰富表达，以及反映NC细胞错误分化的软骨样ECM [7]。重要的是，瘢痕疙瘩来自黑人加勒比皮肤，尽管种族如何影响真皮ECM尚不清楚。需要对区域皮肤差异的机制进行理解;健康面部皮肤的特殊愈合特性有助于改善伤口结果和基于ECM的年轻化技术。此外，比较不同种族的皮肤在伤口愈合方面的差异可能有助于解释为什么存在差异。该项目将揭示皮肤重塑的解剖学差异，并比较高加索人和非洲加勒比人的皮肤。我们的目标是确定可能被利用来改善伤口愈合结果的途径和分子，包括皮肤再生应用。

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.