αvβ3整蛋白作为纤维化和甲状腺激素在全身性硬化症的发展之间的联系
Maia Yamila Kohon1,2, Mor Zaaroor Levy1,2, Tzipi Hornik-Lurie3
1Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
International journal of molecular sciences
|May 27, 2023
概括
占据甲状腺激素结合部位的αvβ3整体素可能会抑制系统性硬化症 (SSc) 中的纤维化发育. 这项研究探讨了αvβ3整合素在纤维化过程中的作用,并发现了潜在的治疗点.
科学领域:
- 免疫学和自身免疫性疾病
- 细胞生物学和细胞外矩阵
- 内分泌学和甲状腺激素信号传递
背景情况:
- 系统性硬化症 (SSc) 是一种由皮肤和器官纤维化标志的自身免疫性疾病.
- 由TGFβ驱动的肌纤维细胞产生细胞外基质 (ECM),这是一个关键的纤维化过程.
- 肌纤维细胞表达αvβ3整合素和miRNA-21,影响甲状腺激素 (TH) 降解和纤维化.
研究的目的:
- 研究甲状腺激素 (TH) 结合部位的αvβ3整合素在纤维化过程中的作用.
- 评估αvβ3整合素调节对纤维细胞行为和SSc.中的纤维细胞标记物的影响.
主要方法:
- 在正常和纤维化细胞外基质 (ECM) 上培养的皮肤纤维细胞 (DF) 有/没有四 (αvβ3联结体).
- 评估了亲纤维性特征,αvβ3整体蛋白,miRNA-21和神酶-3 (D3) 水平.
- 在SSc患者中分析了血液自由T3 (fT3),miRNA-21和修改的罗丹皮肤评分 (MRSS).
主要成果:
- 纤维性ECM显著增加了DFs中的亲纤维性特征,αvβ3,miRNA-21和D3.
- 泰特拉克治疗抑制了纤维化ECM效应,减少了亲纤维化标记物,并使miRNA-21/D3水平正常化.
- 在SSc患者中,FT3和miRNA-21水平与肺动脉高血压 (PAH) 的发展之间存在负相关性.
结论:
- αvβ3整蛋白的TH结合部位在调解SSc纤维化中起着至关重要的作用.
- 准αvβ3整合蛋白TH结合部位的带,如四,可能提供一种治疗策略,以延迟纤维化.
- 调节αvβ3整合素活性可能会影响SSc进展和相关并发症,如PAH.
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