Sirimahachaiyakul Pornthep, Sood Ravi F, Muffley Lara A, Seaton Max, Lin Cheng-Ta, Qiao Liang, Armaly Jeffrey S, Hocking Anne M, Gibran Nicole S
University of Washington Department of Surgery, Seattle, Washington, United States of America.
PLoS One. 2015 Sep 29;10(9):e0139135. doi: 10.1371/journal.pone.0139135. eCollection 2015.
Abnormal pigmentation following cutaneous injury causes significant patient distress and represents a barrier to recovery. Wound depth and patient characteristics influence scar pigmentation. However, we know little about the pathophysiology leading to hyperpigmentation in healed shallow wounds and hypopigmentation in deep dermal wound scars. We sought to determine whether dermal fibroblast signaling influences melanocyte responses.
Epidermal melanocytes from three Caucasians and three African-Americans were genotyped for single nucleotide polymorphisms (SNPs) across the entire genome. Melanocyte genetic profiles were determined using principal component analysis. We assessed melanocyte phenotype and gene expression in response to dermal fibroblast-conditioned medium and determined potential mesenchymal mediators by proteome profiling the fibroblast-conditioned medium.
Six melanocyte samples demonstrated significant variability in phenotype and gene expression at baseline and in response to fibroblast-conditioned medium. Genetic profiling for SNPs in receptors for 13 identified soluble fibroblast-secreted mediators demonstrated considerable heterogeneity, potentially explaining the variable melanocyte responses to fibroblast-conditioned medium.
Our data suggest that melanocytes respond to dermal fibroblast-derived mediators independent of keratinocytes and raise the possibility that mesenchymal-epidermal interactions influence skin pigmentation during cutaneous scarring.
皮肤损伤后的色素沉着异常给患者带来极大困扰，也是恢复的障碍。伤口深度和患者特征会影响瘢痕色素沉着。然而，对于导致愈合的浅表伤口色素沉着过度以及真皮深层伤口瘢痕色素脱失的病理生理学，我们了解甚少。我们试图确定真皮成纤维细胞信号传导是否会影响黑素细胞反应。
对三名白种人和三名非裔美国人的表皮黑素细胞进行全基因组单核苷酸多态性（SNP）基因分型。使用主成分分析确定黑素细胞遗传图谱。我们评估了黑素细胞对真皮成纤维细胞条件培养基的表型和基因表达，并通过对成纤维细胞条件培养基进行蛋白质组分析来确定潜在的间充质介质。
六个黑素细胞样本在基线时以及对成纤维细胞条件培养基的反应中，表型和基因表达存在显著差异。对13种已鉴定的可溶性成纤维细胞分泌介质的受体中的SNP进行基因分型，结果显示出相当大的异质性，这可能解释了黑素细胞对成纤维细胞条件培养基的反应差异。
我们的数据表明，黑素细胞对真皮成纤维细胞衍生的介质有反应，且独立于角质形成细胞，并增加了间充质 - 表皮相互作用在皮肤瘢痕形成过程中影响皮肤色素沉着的可能性。
