白癜风表皮黑素细胞超微结构及小眼畸形相关转录因子转录调控研究

Ultrastructure and transcriptional activity of MITF in epidermal melanocytes from patients with vitiligo

目的 研究白癜风黑素细胞超微结构和小眼畸形相关转录因子（MITF）及其转录调控的酪氨酸酶相关蛋白（TRP）与白癜风临床类型与病程的相关性.方法 选择不同病程的寻常型白癜风（VV）12例和节段型白癜风（SV）8例,分别取白斑区、白斑边缘正常肤色区和远离白斑正常肤色区的表皮片,经组织学确定其表皮的完整性.透射电镜观察10例患者（VV 6例,SV 4例）不同区表皮黑素细胞的超微结构特点.对所有20例远离白斑正常肤色区的表皮片黑素细胞进行培养,应用免疫印迹方法检测MITF及其转录调控的酪氨酸酶（TYR）、酪氨酸酶相关蛋白1（TYRP1）和酪氨酸酶相关蛋白2（TYRP2）的表达水平.结果 白癜风表皮黑素细胞超微结构病理改变：10例中7例白斑区表皮内未见黑素细胞,1例短病程和2例长病程VV分别可见少量黑素体显著减少或缺失的黑素细胞;白斑边缘正常肤色区,6例VV中,3例病程小于15个月者可见黑素细胞超微结构异常,而4例SV中仅1例异常;远离白斑正常肤色区,10例黑素细胞超微结构均正常.白癜风表皮黑素细胞MITF及其转录调控TRP的表达：VV的MITF表达下调与TYR、TYRP1、TYRP2的表达下调一致;SV存在MITF显著表达下调.而TYR、TYRP1、TYRP2几均正常表达.结论 VV和SV可能存在不同的表皮黑素细胞超微结构病理改变和MITF转录调控机制.

Objective To analyze the relationship of melanocyte ultrastructure and expression of microphthalmia-associated transcription factor （MITF） as well as tyrosinase-related proteins （TRP） transcriptionally modulated by MITF to clinical types and duration of vitiligo.Methods Epidermal sheets were taken by suction blisters respectively from lesional,perilesional,and normal skin of 12 patients with vitiligo vulgaris （VV） and 8 with segmental vitiligo （SV）.The duration of vitiligo varied from 3 to 300 months in these patients. Transmission electron microscopy was performed in 10 patients with vitiligo,including 6 cases of VV and 4 cases of SV.Epidermal melanocytes from normal skin of 20 patients were subjected to culture followed by Western blot to detect the expression level of MITF and some molecules transcriptionally modulated by MITF,including tyrosinase （TYR）,TYR-related protein-1（TYRP1）,and TYR-related protein-2 （TYRP2） in cultured melanocytes.Results Epidermal melanocytes were absent in lesional skin of 7 out of 10 patients observed for ultrastructural alterations,whereas melanocytes with reduced or absent melanin （melanosome） could accidently be seen in lesional skin of 1 patient with short-standing vitiligo and 2 patients with long-standing vitiligo.In perilesional skin.abnormal ultrastructure of melanocytes was found in 3 with a duration of vitiligo less than 15 months among 6 patients with VV,and in 1 out of 4 patients with SV.The down-regulated expression of MITF was consistent with that of TYR,TYRP1 and TYRP2 in cultured epidermal melanocytes from normal skin of patients with VV;in those from patients with SV,the down-regulated expression was observed only in MITF,while the expressions of TYR,TYRP1 and TYRP2 were nearly normal.Conclusion Differences may exist between VV and SV in the ultrastructure as well as mechanisms of transcriptional modulation by MITF in epidermal melanocytes.