Gene expression in human keloids is altered from dermal to chondrocytic and osteogenic lineage
Gene expression in human keloids is altered from dermal to chondrocytic and osteogenic lineage
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DOI：
10.1111/j.1365-2443.2005.00902.x
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发表时间：
2005-11-01
期刊：
影响因子：
2.1
通讯作者：
Nagata, K
中科院分区：
文献类型：
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作者：
Naitoh, M;Kubota, H;Nagata, K
瘢痕疙瘩是一种皮肤纤维化疾病，其病因仍然完全未知，并且没有成功的治疗方法。在这里，我们采用基因芯片分析，以研究基因表达在瘢痕疙瘩病变和对照皮肤。我们发现在9000个检测基因中有32个在瘢痕疙瘩病变中强烈上调，其中21个通过北方印迹证实。这些包括至少7个软骨细胞/成骨细胞标记基因，RT-PCR分析显示，这些基因，SOX 9和CBFA 1，特异性的转录因子被诱导。免疫染色和原位杂交进一步支持这些标记物在瘢痕疙瘩病变中表达。有趣的是，巩膜轴，一种被称为肌腱和韧带标记的转录因子，也在瘢痕疙瘩成纤维细胞中被诱导。我们提出，基因表达的重新编程或从真皮模式到软骨细胞/成骨谱系的无序分化，可能更接近肌腱/韧带谱系，可能参与瘢痕疙瘩的病因学。
Keloids are a dermal fibrotic disease whose etiology remains totally unknown and for which there is no successful treatment. Here, we employed cDNA microarray analysis to examine gene expression in keloid lesions and control skin. We found that 32 genes among the 9000 tested were strongly up-regulated in keloid lesions, of which 21 were confirmed by Northern blotting. These included at least seven chondrocyte/osteoblast marker genes, and RT-PCR analysis revealed that transcription factors specific for these genes, SOX9 and CBFA1, were induced. Immunostaining and in situ hybridization further supported that these markers are expressed in keloid lesions. Intriguingly, scleraxis, a transcription factor known as a marker of tendons and ligaments, was also induced in keloid fibroblasts. We propose that reprogramming of gene expression or disordered differentiation from a dermal pattern to that of a chondrocytic/osteogenic lineage, probably closer to that of tendon/ligament lineage, may be involved in the etiology of keloids.