Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia.
Department of Biochemistry and Molecular and Cellular Biology, Georgetown University School of Medicine, Washington, District of Columbia.
Pigment Cell Melanoma Res. 2019 Sep;32(5):643-656. doi: 10.1111/pcmr.12780. Epub 2019 Apr 5.
Although pigment synthesis is well understood, relevant mechanisms of psychologically debilitating dyspigmentation in nascent tissue after cutaneous injuries are still unknown. Here, differences in genomic transcription of hyper- and hypopigmented tissue relative to uninjured skin were investigated using a red Duroc swine scar model. Transcription profiles differed based on pigmentation phenotypes with a trend of more upregulation or downregulation in hyper- or hypopigmented scars, respectively. Ingenuity Pathway Analysis of significantly modulated genes in both pigmentation phenotypes showed pathways related to redox, metabolic, and inflammatory responses were more present in hypopigmented samples, while those related to stem cell development differentiation were found mainly in hyperpigmented samples. Cell-cell and cell-extracellular matrix interactions and inflammation responses were predicted (z-score) active in hyperpigmented and inactive in hypopigmented. The proinflammatory high-mobility group box 1 pathway showed the opposite trend. Analysis of differentially regulated mutually exclusive genes showed an extensive presence of metabolic, proinflammatory, and oxidative stress pathways in hypopigmented scars, while melanin synthesis, glycosaminoglycans biosynthesis, and cell differentiation pathways were predominant in hyperpigmented scar. Several potential therapeutic gene targets have been identified.
虽然色素合成机制已被充分了解，但皮肤损伤后新生组织中导致心理性色素脱失的相关机制仍不清楚。本研究通过红色杜洛克猪瘢痕模型，研究了与未受伤皮肤相比，超色素和低色素组织的基因组转录差异。转录谱因色素沉着表型的不同而存在差异，超色素和低色素瘢痕分别呈现出更多的上调或下调趋势。对两种色素沉着表型中显著调节基因的 IPA 分析显示，低色素样本中存在与氧化还原、代谢和炎症反应相关的途径，而高色素样本中则存在与干细胞发育分化相关的途径。细胞-细胞和细胞-细胞外基质相互作用以及炎症反应被预测（z 评分）在高色素样本中活跃，而在低色素样本中不活跃。促炎高迁移率族蛋白 1 途径则呈现出相反的趋势。对差异调节的互斥基因的分析表明，低色素瘢痕中存在广泛的代谢、促炎和氧化应激途径，而高色素瘢痕中则以黑色素合成、糖胺聚糖生物合成和细胞分化途径为主。已经确定了几个有潜在治疗作用的基因靶点。
