Cthrc1/ TGF-β1对系统性硬皮病纤维化调控机制的研究

Mammalian collagen triple helix repeat containing protein 1(Cthrc1) is a recently found gene product with novel biological activities, which involved in the arterial injury repair process by reducing collagen deposition and increasing cell migration. Our previous study for the first time illustrated the interaction between Cthrc1 and TGF-β 1 in the keloid fibroblasts, we found that cthrc1 could inhibit type I collagen expression induced by TGF-β1, which suggest cthrc1 as a powerful regulator of reducing collagen matrix deposition, has the important application prospect in the antifibrosis treatment. Systemic sclerosis (SSc) is a severe, immune-mediated disorder with fibrosis of the skin and visceral organs. For now, without any effective therapy. Our research proposed to explore the regulatory role of Cthrc1/TGF-β1 on the oxidative stress and Th17 cells based on the previous study, further clarify the pathogenesis of SSc and provide a new idea for effective anti-fibrosis treatment.

哺乳动物胶原三螺旋重复蛋白1（ Collagen triple helix repeat containing protein 1，Cthrc1）是新近发现的一种具有新颖生物学活性的基因产物，它通过抑制胶原基质的沉积和促进细胞迁移参与了血管的损伤修复过程。我们的前期研究在国内外首次阐明瘢痕疙瘩成纤维细胞中Cthrc1与TGF-β1间的相互作用，发现Cthrc1可抑制TGF-β1诱导的I型胶原的表达，提示Cthrc1 作为一种强效的抑制胶原基质沉积的调节剂，在抗纤维化治疗中具有重要的应用前景。系统性硬皮病(Systemic Sclerosis,SSc)是一种导致皮肤和内脏器官纤维化的自身免疫性疾病。对其治疗目前尚无特效的药物。本课题拟在前期工作基础上研究Cthrc1/TGF-β1对氧化应激和Th17细胞在SSc纤维化中的调控作用，进一步阐明硬皮病的发病机理，为有效抗纤维化治疗提供新的思路。