瘢痕疙瘩成纤维细胞的基因组学研究

目的 寻找瘢痕疙瘩致病相关基因，探讨瘢痕疙瘩的发生机理。方法 利用含1100个人类肿瘤相关基因的cDNA芯片(cDNA—microarray)对耳垂和胸部瘢痕疙瘩及正常皮肤成纤维细胞进行检测，初步分析瘢痕疙瘩成纤维细胞与正常皮肤成纤维细胞基因总体表达的差异，并筛选出差异基因。结果 在耳垂及胸部瘢痕疙瘩成纤维细胞中，分别有8种和17种特异性表达基因被检出。在正常皮肤中特异性表达的细胞增殖抑制基因Mda-7，在耳垂及胸部瘢痕疙瘩成纤维细胞中均未被表达。结论 多种基因参与了瘢痕疙瘩的形成过程，瘢痕疙瘩成纤维细胞与正常皮肤成纤维细胞之间存在基因表达的差异，增殖因子受体PAR-1和增殖抑制基因Mda-7可能参与瘢痕疙瘩的形成。

Pathological genomics of keloid fibroblastic cells

Objective Keloids result from the abnormal repair of the tissues after skin injuries where the pathological overgrowth of large and active fibroblastic cells expands beyond the boundaries of the initiating wound. Imbalanced expression of genes with an as yet unknown regulatory mechanism seems to result in the hypertrophic development of fibroblastic cells and over-productions of collagen. To get information as to genes which function in the actively growing keloid fibroblasts, we have applied a gene expression DNA-microarray technique by analyzing broad range of genes at once in a systematic fashion. Methods Differential gene expressions of keloid fibroblastic cell lines against a normal skin fibroblastic cell line, all of the cell lines had been propagated in our lab, were analyzed using a cDNA-microarray technique. mRNA was extracted from the control normal skin cells and the two lines of keloid fibroblastic cells, one from ear-lobe keloid tissue and the other from chest keloid tissue, was subjected to a DNA microarray analysis which includes 1 100 human genes (TaKaRa IntelliGene Human CHIP 1K Set I). Results 8 genes were found to be expressed exclusively in ear-lobe keloid fibroblastic cell lines. Cells from chest keloid were detected to express 17 genes, specifically. Coagulation factor II (thrombin) receptor gene, KIAA0367 protein gene, and matrilin-2 gene were found to be the most commonly expressed genes in the keloid cells. Suppressor genes, like melanoma differentiation associated gene-7, Mda-7 (U16261), were expressed in normal skin fibroblasts but were not expressed in keloid fibroblasts may be implicated in the pathogenesis of the keloid lesions. Conclusions Genes expressed specifically in keloid cells may be an adequate pathological diagnostic marker for keloids. Further, Identification of genes that cause cells to develop keloid lesions leads us to gene therapy and prevention of keloids.