Studying Of Gene Mutation Of Keloid

Keloids are the result of a dysregulated wound healing process. They are characterized by the formation of excess scar tissue that proliferates beyond the boundaries of the original wound. The treatment of keloid is one of the most troublesome subject in Plastic surgery. Some progress about the mechanism of keloid have been maken in recent years , but we couldn抰 explain how keloid formed ultimately until now. Purpose: From our previous study, the fibroblasts derived from k閘oid showed highly expressed Fas antigen and P53 protein, but it resisted to apoptosis induced by FasMcab and loss the function of resraining cell process of P53 protein in contrast to hypertrophic scars and normal skins. It was very significant for Fas antigen and P53 protein to physiological apoptosis, preventing mutation accumulating and suppressing tumor emerging. The Fas antigen and P53 protein of fibroblasts derived from keloid loss their physiological function and closely connected with the formation of keloid. In this study, in order to clarify molecular mechanism of the formation keloid, we detected disorder of Fas gene and P53 gene (exon 4- 6) in fibroblasts of tissues from skin lesions of 15 patients with keloids. Method: Keloids and hypertrophic scar tissue and the peripheral blood of each patient were collected. After DNA isolated from the samples,we used 6 the single-stranded conformation polymorphism analysis and DNA sequencing, to examined the structure of the Fas gene and P53 gene. Result: Loss of heterozygosis (LOH) in Fas gene exon 8 and mutations in P53 exon 4 were identified in all patients with keloids by PCR-SSCP. Mutations were found in Fas intron 5 , Fas exon 9, P53 exon 5-6 respectively in 2 ,3 and 8 patients, No Fas mutations were found in fibroblasts from normal skin samples and in peripheral blood cell of any of the patients. Gene sequencing proved these mutations. Coi~clusion: LOH in exon 8 and mutation in exon 9 resulted in keloid Fas protein with incomplete deathdoman and closely connected with its nonfunction. P53 gene mutation resulted in changing of P53 protein ,mutant protein accumulating increased the cellular stability which in turn may lead to an alterd balance between apoptosis and the proliferation of keloid fibroblasts. No Fas mutations were found in fibroblasts from normal skin samples ~nd in peripheral blood cell of any of the patients, it indicated that these gene mutation belonged to somatic mutation, Fas exon 8 and P53 expn4 were chief position of gene mutation. Focal mutations in Fas and P53 may increase cell proliferation and decrease cell death in the dysregulated groth patterns, an further study of these two protein may lead to make clear the molecular biology of keloid...