Gene expression patterns in isolated keloid fibroblasts
Gene expression patterns in isolated keloid fibroblasts
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DOI：
10.1111/j.1743-6109.2006.00135.x
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发表时间：
2006-07-01
影响因子：
2.9
通讯作者：
Wells, Alan
中科院分区：
文献类型：
--
作者：
Satish, Latha;Lyons-Weiler, James;Wells, Alan
皮肤外伤后的疤痕疙瘩是一个重要的临床问题，尤其是在黑人群体中，疤痕疙瘩的发病率估计为 4-16%。疤痕疙瘩是继发于伤口愈合失调的异常真皮增生性疤痕。尽管对细胞外基质蛋白和生长因子在疤痕疙瘩形成过程中的作用进行了多项生化研究，但我们仍然不知道是什么分子和信号诱导了这种变化。成纤维细胞被认为是疤痕疙瘩形成的主要诱导细胞。本研究的目的是确定表征瘢痕疙瘩成纤维细胞的基因表达模式；识别这种遗传不平衡可能有助于揭示导致疤痕疙瘩形成的分子信号传导事件。在本研究中，我们使用 Affymetrix U133a 芯片（22,284 个基因和表达序列标签）对从三个个体的瘢痕疙瘩病变中分离的成纤维细胞与从正常皮肤分离的成纤维细胞进行了基因表达分析。我们通过J5测试得分表达分析发现，与无疤痕疙瘩者的真皮成纤维细胞相比，在22,284个基因中，有43个基因在疤痕疙瘩成纤维细胞中过度表达，有5个基因表达不足。实时聚合酶链式反应证实了先前未报道的在瘢痕疙瘩中上调的三个基因（膜联蛋白 A2、Transgelin 和 RPS18）的过度表达。某些过度表达的基因与之前在瘢痕疙瘩形成过程中对这些过度表达的基因的蛋白质水平的生化观察结果相似。我们还首次报道了一些肿瘤相关基因在瘢痕疙瘩成纤维细胞中过度表达。
Keloid scars after skin trauma are a significant clinical problem, especially in black populations, in which the incidence of keloids has been estimated at 4-16%. Keloids are abnormal dermal proliferative scars secondary to dysregulated wound healing. Despite several biochemical studies on the role of extracellular matrix proteins and growth factors during keloid formation, we still do not know what molecules and signals induce this change. Fibroblasts are thought to be the major inductive cell for keloid scar formation. The aim of this study was to identify gene expression patterns that characterize keloid fibroblasts; identifying such genetic disequilibrium may shed light on the molecular signaling events responsible for keloid formation. In this study, we performed gene expression analysis of fibroblasts isolated from keloid lesions from three individuals in comparison with the fibroblasts isolated from normal skin using the Affymetrix U133a chip (22,284 genes and expression sequence tags). We found through J5 test score expression analysis that among 22,284 genes, there were 43 genes that were overexpressed and five genes were underexpressed in keloid fibroblasts when compared with dermal fibroblasts from persons without keloids. The overexpression of three genes not previously reported as being up-regulated in keloids (annexin A2, Transgelin, and RPS18) was confirmed by real-time polymerase chain reaction. Certain overexpressed genes were similar to previous biochemical observations on the protein levels of these overexpressed genes during keloid formation. We also report for the first time that a few tumor-related genes are overexpressed in keloid fibroblasts.