KIF1C和新的亨廷丁相互作用蛋白1结合蛋白调节类风湿性关节炎纤维细胞样同胞细胞的表型
Teresina Laragione1, Carolyn Harris1, Percio S Gulko1
1Division of Rheumatology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Frontiers in immunology
|May 10, 2024
概括
研究人员发现了与亨廷相互作用蛋白-1 (HIP1) 结合的新蛋白质,揭示了类风湿性关节炎 (RA) 的潜在治疗点. 这些HIP1结合蛋白调节关键的纤维细胞样同胞细胞 (FLS) 行为,有助于RA的发病.
科学领域:
- 分子生物学分子生物学
- 类风湿病学 类风湿病学
- 细胞生物学 细胞生物学
背景情况:
- 亨廷丁相互作用蛋白-1 (HIP1) 与类风湿性关节炎 (RA) 严重程度有关.
- HIP1调节了RA纤维细胞样同胞细胞 (FLS) 的入侵性质,与关节损伤相关.
- 了解HIP1的绑定伙伴对于阐明其在FLS入侵中的作用和确定治疗点至关重要.
研究的目的:
- 为了识别新的HIP1结合蛋白.
- 研究这些结合蛋白对RA FLS表型的功能影响.
- 探索潜在的RA的新治疗策略.
主要方法:
- 从关节炎和受保护的老鼠培养的FLS细胞系在HIP1单核酸多态 (SNP) 中有所不同.
- HIP1的免疫沉,然后进行质谱测量以确定结合蛋白.
- 人类RAFLS中候选蛋白质的siRNA敲除,以评估对侵入性,粘附性,迁移和增殖的影响.
- 免疫光显微镜分析蛋白质定位和细胞形态.
主要成果:
- 确定已知的和新的HIP1结合蛋白.
- 四十五种蛋白质在老鼠FLS系之间显示出差异的丰度.
- 10种蛋白质的淘汰显著改变了RA FLS表型,其中五种侵袭性下降 (CHMP4BL1,COPE,KIF1C,YWHAG,YWHAH).
- KIF1C的淘汰减少了迁移,改变了FLS形态,影响了独立于Rac1信号的actin组织和lamellipodia形成.
结论:
- 发现了新的HIP1结合蛋白,调节关键的RA FLS功能.
- 这些HIP1结合蛋白代表了RA的潜在治疗点.
- KIF1C在RA FLS形态和入侵中发挥作用,与HIP1已知的信号通路不同.
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