A Signature of Genes Featuring FGF11 Revealed Aberrant Fibroblast Activation and Immune Infiltration Properties in Keloid Tissue

Abstract

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.

An updated review of the immunological mechanisms of keloid scars

“…The concept of keloid microenvironment has been frequently evoked to describe the complex cellular and molecular interplay that gives rise to and sustains keloidogenesis. Recent technologies, such as identification of differentially expressed genes via examination of RNA sequencing data sets ( 74 , 75 , 78 – 80 ), have led to more extensive analysis of keloid tissue. A skewed T helper (Th) 2 phenotype was recently characterized ( 81 – 85 ), along with a potential co-susceptibility of keloids and atopic dermatitis ( 6 , 12 , 86 ).…”

Retracted: A Signature of Genes Featuring FGF11 Revealed Aberrant Fibroblast Activation and Immune Infiltration Properties in Keloid Tissue

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process: Discrepancies in scope Discrepancies in the description of the research reported Discrepancies between the availability of data and the research described Inappropriate citations Incoherent, meaningless and/or irrelevant content included in the article Manipulated or compromised peer review …”

“…Tis article has been retracted by Hindawi following an investigation undertaken by the publisher [1]. Tis investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process:…”