瘢痕疙瘩中TIEG1的高表达
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广东省自然科学基金(7001657)和广东省医学科研基金(B2007042)资助项目.


Increased Expression of TGF-β Inducible Early Gene (TIEG1) in Keloid Scarrin
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    摘要:

    转化生长因子-β1(TGF-β1/Smads)信号转导通路的持续激活是瘢痕疙瘩形成的重要机制. 研究发现这条通路重要的负反馈调节信号分子Smad7表达明显下调,Smad2/3的磷酸化水平和蛋白质量并无明显改变. 但是,Smad7下调的机制尚不清楚. 采用生物信息学方法对Smad7的启动子进行分析;用RT-PCR和蛋白质印迹分别检测了正常皮肤、正常瘢痕及瘢痕疙瘩组织中的Sp1样转录因子TIEG1 mRNA及蛋白质的表达水平;体外培养正常皮肤、正常瘢痕及瘢痕疙瘩成纤维细胞,检测TIEG1 mRNA及蛋白的表达水平. 研究结果显示,Smad7启动子上有Sp1的位点,TIEG1 mRNA及蛋白质水平在瘢痕疙瘩组织及瘢痕疙瘩成纤维细胞中表达明显高于正常瘢痕和正常皮肤 (P < 0.05). 说明瘢痕疙瘩中TIEG1可能是Smad7下调的重要原因,有必要进一步研究TIEG1对Smad7的调控作用机制.

    Abstract:

    The transforming growth factor (TGF)-beta/Smad signaling pathway is thought to play a major role in keloid formation. This study showed that the expression of inhibitory Smad7 was significantly down regulated in keloid compared with normal scar (P < 0.05) and normal skin (P < 0.05), however, no significant difference of Smad2 , 3 and the phosphorylation of Smad2,3. But the mechanism of reduced expression of Smad7 is unclear. Sp1 binding sites were found in Smad7 promotor by bioinformatics system analysis, then, the expression of TIEG1 mRNA and proteins in keloids, in normal skin and in normal scars tissues and fibroblasts were investigated. Dermal fibroblasts were obtained from biopsies of keloids, normal scars and normal skin. Fibroblasts were cultured in vitro. The expression of TIEG1 mRNA was analysed by RT-PCR and protein expression was determined by Western blot analysis. The results demonstrated increased mRNA and protein expressions of TIEG1 in keloid tissue and fibroblasts as compared to normal scar tissues and fibroblasts (P < 0.05) and normal skin tissues and fibroblasts (P < 0.05). It suggested that TIEG1 might play a significant role to the decreased expression of the inhibitory Smad7 in keloid. Further investigation is necessary to illuminate the mechanism of TIEG1 regulating Smad7.

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唐冰,朱家源,朱斌,刘阳,李新强,毕良宽.瘢痕疙瘩中TIEG1的高表达[J].生物化学与生物物理进展,2007,34(10):1033-1039

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历史
  • 收稿日期:2007-08-06
  • 最后修改日期:2007-09-28
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  • 在线发布日期: 2007-10-22
  • 出版日期: 2007-10-20