增生性瘢痕形成和成熟过程中TGF-β_1及其下游信号分子的基因表达变化

Gene expression of TGF-β_1 and its downstream signal molecules in proliferative and mature hypertrophic scars

目的:探讨转化生长因子-β_1(TGF-β_1)及其下游信号分子 smad2,smad3和 smad4在伤后不同时期的增生性瘢痕组织中的表达变化规律及其可能的生物学意义。方法:用病理学技术检测增生性瘢痕和正常皮肤的结构特征后,提取16例不同发生时期的增生性瘢痕(4个月～11年)和8例正常皮肤组织的总 RNA 后,分离mRNA,用 RT-PCR 方法检测这4种基因在不同组织中的表达变化规律。结果:TGF-β_1,smad2,smad3和smad4基因在正常皮肤和增生性瘢痕中都有表达。TGF-β_1在不同类型组织中表达水平相近似。与正常皮肤相比,smad2,smad3和 smad4基因的转录本含量在增殖期的增生性瘢痕中明显升高,在成熟期的增生性瘢痕中smad2基因表达量恢复到正常皮肤水平,而 smad3和 smad4基因表达虽有所减弱,但两种基因的 mRNA 含量仍明显高于正常皮肤(P<0.05)。结论:信号分子 smad2,smad3和 smad4基因表达增强可能是增生性瘢痕形成的机制之一,而 smad2表达降低,其介导的信号通路减弱可能与增生性瘢痕达到相对稳定的成熟状态有关,而TGF-β_1在增生性瘢痕形成过程中的作用需进一步研究。

Objective:To investigate the changes in gene expression of transforming growth factor-beta_1(TGF- β_1)and its downstream signal molecules(smad2,smad3 and smad4)in normal skin versus hypertrophic sears, and their underlying its biological significance.Methods:After morphological characteristics of hypertrophic scars at different periods after wounding and normal skin were identified at pathological methods,total RNA was extrac- ted from 16 specimens of hypertrophic scars and 8 specimens of normal skin,and then RNA was purified to mR- NA.Gene expression of TGF-β_1,smad2,smad3 and smad4 were determined with reverse transcription-polymer- ase chain reaction(RT-PCR).Results:Gene expressions of TGF-β_1,smad2,smad3 and smad4 could all be detec- ted in normal skin and hypertrophic scars.The level of gene expression of TGF-β_1in various samples was relative similar.In comparison with normal skin,the content of transcript of smad2 was apparently enhanced in prolifera- tive scars,and decreased to the level similar to that of normal skin in mature scars.Gene expressions of smad3 and smad4 were significantly elevated in hypertrophic scars at different periods after wounding compared with normal skin(P<0.05).Conclusion:The elevation of in gene expression of smad2,smad3 and smad4 might be involved in the formation of hypertrophic scar,while lowering of smad2 gene expression may be associated with hypertrophic scar approaching mature status.The role of TGF-β_1 in formation of hypertrophic scar needs to be further studied.