Keloid is a fibroproliferative disorder in the skin, which manifested with extensive deposition of collagen and extracellular matrix. Its etiology remains a mystery and its recurrence rate remains high despite combinative treatment regimens. Current hypotheses of its pathogenesis centered on the role of inflammatory processes as well as immune infiltration in the microenvironment. However, there are a lot of discrepancies when it comes to the verification of certain well-recognized pathways involved in the dysfunctional fibroblast. Further exploration and characterization are required to reveal the driving force and even leading genes responsible for keloid formation. In this study, we provided supportive evidence of the immunologic nature of keloids distinct from normal fibroblasts and physiological scars by incorporating multiple available expressional profiles in the Gene Expression Omnibus (GEO). Through differential analyses and functional analyses, we identified a set of genes that successfully captures the dissimilarities between keloid lesions and nonlesions. They were differentially regulated in keloid samples and had opposite behavior in exposure to hydrocortisone. A key signature of six genes featuring FGF11 not only was highly correlated with significantly dysregulated fibroblast activation but also reflected various levels of immune cell infiltration. FGF11, in particular, revealed the heterogenous immunologic nature of keloid lesions. This study further supported that aberrant fibroblast was one of the main contributing factors and shed some light on investigating immune properties in future studies.

中文翻译：

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具有 FGF11 的基因特征揭示了瘢痕疙瘩组织中的异常成纤维细胞活化和免疫浸润特性

瘢痕疙瘩是一种皮肤纤维增生性疾病，表现为胶原蛋白和细胞外基质的广泛沉积。尽管有联合治疗方案，其病因仍然是一个谜，其复发率仍然很高。目前对其发病机制的假设集中在炎症过程的作用以及微环境中的免疫浸润。然而，在验证某些公认的参与功能失调的成纤维细胞的途径时，存在很多差异。需要进一步探索和表征以揭示导致瘢痕疙瘩形成的驱动力甚至主导基因。在这项研究中，我们通过在 Gene Expression Omnibus (GEO) 中整合多种可用的表达谱，提供了与正常成纤维细胞和生理性疤痕不同的瘢痕疙瘩免疫学性质的支持性证据。通过差异分析和功能分析，我们确定了一组成功捕捉瘢痕疙瘩病变和非病变之间差异的基因。它们在瘢痕疙瘩样本中受到不同的调节，并且在暴露于氢化可的松时具有相反的行为。六个基因的关键特征 它们在瘢痕疙瘩样本中受到不同的调节，并且在暴露于氢化可的松时具有相反的行为。六个基因的关键特征 它们在瘢痕疙瘩样本中受到不同的调节，并且在暴露于氢化可的松时具有相反的行为。六个基因的关键特征FGF11不仅与显着失调的成纤维细胞活化高度相关，而且反映了不同水平的免疫细胞浸润。特别是FGF11揭示了瘢痕疙瘩病变的异质免疫性质。该研究进一步支持异常成纤维细胞是主要促成因素之一，并为在未来研究中研究免疫特性提供了一些启示。