fas基因和p53基因在瘢痕疙瘩成纤维细胞中的结构异常与其功能的关系

Abnormal structure of fas and p53 gene in keloid-derived fibroblasts and their function

目的:人体内瘢痕疙瘩成纤维细胞对生长因子的需要量,以及对生长抑制因子的反应都与正常成纤维细胞不同。探讨fas基因和p53基因在瘢痕疙瘩成纤维细胞中的结构变化与其功能的关系。方法:实验于2001-03/09在解放军第一军医大学热带病研究所完成。采用聚合酶链反应-单链构象多态性及基因测序技术,以增生性瘢痕及正常皮肤为对照,检测瘢痕疙瘩组织标本中成纤维细胞fas全基因编码序列和p53基因突变高发区外显子4～6的基因结构,以其变化判断在瘢痕形成中抑制细胞进程及介导细胞凋亡的功能。结果:瘢痕疙瘩fas基因外显子6,8,9及p53基因外显子4,5,6均存在突变,对照组未发现突变。结论:正常皮肤fas和p53基因结构无变异,瘢痕疙瘩成纤维细胞fas基因和p53基因外显子的突变,致介导细胞凋亡及抑制细胞进程等功能丧失,与瘢痕疙瘩的形成有关。

AIM:Human keloid- derived fibroblasts' need for the growth factors in quanti ty and their responses to the growth inhibitors are different from normal fibrob lasts'.We investigated the structural changes of fas gene(exon 1- 9) and p53 ge ne(exon 4- 6) in keloid fibroblasts associated with their function in this stud y. METHODS:The experiment was conducted in the Department of Tropical Diseases,F irst Military Medical University from March to September 2001.The polymerase cha in reaction followed by single- strand conformational polymorphism analysis and DNA sequencing were used to detect the changes of total coding sequence of fas gene and the structure of exons 4,5,6 in frequent p53 gene mutation area in the fibroblasts derived from the keloid specimens in order to verify their roles in suppressing cell growth and mediating cell apoptosis in the formation of keloid, using hyperplastic scar and normal skins as controls. RESULTS:Gene mutations in fas gene(exons 6,8 ,9) and p53 gene(exons 4,5,6) we re identified in all patients with keloids,but those in the controls were not fo und. CONCLUSION:The structure of fas gene and p53 gene were found still normal.The exon mutations of fas gene and p53 gene in keloid- derived fibroblasts result in their functional loss such as suppression of cell growth,mediation of cell ap optosis,which is associated with the formation of keloid.