胶原三螺旋重复蛋白1抑制TGF-β1诱导的瘢痕组织Ⅰ型胶原的表达
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摘要
背景瘢痕疙瘩是具有瘢痕体质病人在伤口愈合过程中发生的良性皮肤肿瘤。有研究表明,转化生长因子(TGF-β)参与了瘢痕的形成过程。胶原三螺旋重复蛋白1(Cthrcl)作为一种新型的基因表达于受损动脉的外膜以及内膜。它作为细胞特异性TGF-β抑制剂,通过抑制Ⅰ型和Ⅲ型胶原沉积而增加细胞的迁移功能。然而,目前为止,在瘢痕组织和正常皮肤中,Cthrcl与TGF-β1的表达和调节机制没有得到很好的研究。
目的探索Cthrc1在瘢痕形成过程中的基因调节和潜在功能。以及在瘢痕病理形成过程中与TGF-β1之间的关联。
方法检测瘢痕组织与正常皮肤成纤维细胞中Cthrcl与TGF-β1的表达。并检测TGF-β1诱导下瘢痕成纤维细胞Ⅰ型胶原的表达与合成。应用重组Cthrcl检测其与TGF-β1之间的关联。
结果瘢痕组织,中Cthrcl与TGF-β1的表达均高于正常皮肤组织。瘢痕成纤维细胞中,TGF-β1诱导Cthrc1表达增加呈浓度依赖性。TGF-β1刺激瘢痕成纤维细胞Ⅰ型胶原的表达与合成,重组Cthrc1可抑制上述效应。
结论在瘢痕成纤维细胞中,TGF-β1表达增加并且重组Cthrc1可抑制TGF-β1诱导的Ⅰ型胶原的合成,表明Cthrc1可能作为瘢痕治疗潜在的治疗方法。
Background Keloids are benign skin tumours occurring during wound healing in genetically predisposed patients. There is evidence that transforming growth factor-beta (TGF-β) is involved in keloid formation. Collagen triple helix repeat containing-1 (Cthrcl) was identified as a novel gene expressed in the adventitia and neointima on arterial injury. It is indicated to be a cell type-specific inhibitor of TGF-β, which functionally increases cell migration while reducing collagen type I and III deposition. To our knowledge, however, expression and regulatory mechanisms of Cthrcl and TGF-β1 in keloid and normal skin has not been studied before.
Objectives Cthrcl gene regulation and potential role in keloid formation were determined. And its correlation with TGF-β1 invovled in the keloid pathogenesis was examined in human fibroblasts of keloids and normal skins.
Methods The expression of Cthrcl and TGF-β1were investigated in fibroblasts of keloid and normal skin. The collagen typeⅠexpression and collagen synthesis in keloid fibroblasts induced by TGF-β1 were examined. Then, recombinant Cthrclwas applied to assess its correlation with TGF-β1.
Results Increased TGF-β1 and Cthrcl expression were examined in keloid compared with normal skin. Cthrcl expression increased in a concentration dependent manner induced by TGF-β1 in keloid fibroblasts. TGF-β1 stimulated collagen typeⅠexpression and collagen synthesis in keloid fibroblasts which can be reversed by recombinant Cthrcl.
Conclusions TGF-β1 was upregulated in keloid fibroblasts and recombinant Cthrcl inhibited TGF-β1-stimulated collagen typeⅠsynthesis which suggested Cthrcl may be a potential therapeutic option for keloids.
目的探索Cthrc1在瘢痕形成过程中的基因调节和潜在功能。以及在瘢痕病理形成过程中与TGF-β1之间的关联。
方法检测瘢痕组织与正常皮肤成纤维细胞中Cthrcl与TGF-β1的表达。并检测TGF-β1诱导下瘢痕成纤维细胞Ⅰ型胶原的表达与合成。应用重组Cthrcl检测其与TGF-β1之间的关联。
结果瘢痕组织,中Cthrcl与TGF-β1的表达均高于正常皮肤组织。瘢痕成纤维细胞中,TGF-β1诱导Cthrc1表达增加呈浓度依赖性。TGF-β1刺激瘢痕成纤维细胞Ⅰ型胶原的表达与合成,重组Cthrc1可抑制上述效应。
结论在瘢痕成纤维细胞中,TGF-β1表达增加并且重组Cthrc1可抑制TGF-β1诱导的Ⅰ型胶原的合成,表明Cthrc1可能作为瘢痕治疗潜在的治疗方法。
Background Keloids are benign skin tumours occurring during wound healing in genetically predisposed patients. There is evidence that transforming growth factor-beta (TGF-β) is involved in keloid formation. Collagen triple helix repeat containing-1 (Cthrcl) was identified as a novel gene expressed in the adventitia and neointima on arterial injury. It is indicated to be a cell type-specific inhibitor of TGF-β, which functionally increases cell migration while reducing collagen type I and III deposition. To our knowledge, however, expression and regulatory mechanisms of Cthrcl and TGF-β1 in keloid and normal skin has not been studied before.
Objectives Cthrcl gene regulation and potential role in keloid formation were determined. And its correlation with TGF-β1 invovled in the keloid pathogenesis was examined in human fibroblasts of keloids and normal skins.
Methods The expression of Cthrcl and TGF-β1were investigated in fibroblasts of keloid and normal skin. The collagen typeⅠexpression and collagen synthesis in keloid fibroblasts induced by TGF-β1 were examined. Then, recombinant Cthrclwas applied to assess its correlation with TGF-β1.
Results Increased TGF-β1 and Cthrcl expression were examined in keloid compared with normal skin. Cthrcl expression increased in a concentration dependent manner induced by TGF-β1 in keloid fibroblasts. TGF-β1 stimulated collagen typeⅠexpression and collagen synthesis in keloid fibroblasts which can be reversed by recombinant Cthrcl.
Conclusions TGF-β1 was upregulated in keloid fibroblasts and recombinant Cthrcl inhibited TGF-β1-stimulated collagen typeⅠsynthesis which suggested Cthrcl may be a potential therapeutic option for keloids.
引文
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