储存的Ca2+输入有助于ASM表型在喘中的过渡
Hangqi Ni1, Ting Li1, Junjun Chen1
1Department of Respiratory and Critical Care Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, P.R. China.
Experimental lung research
|April 10, 2025
概括
涉及STIM1和Orai1的储存运行入 (SOCE) 促进呼吸道光滑肌细胞的增殖和喘中的细胞外基质沉积. 抑制SOCE可以减少这些影响,这表明它是气道改造的治疗目标.
科学领域:
- 细胞和分子生物学 细胞和分子生物学
- 呼吸系统医学 呼吸系统医学
- 免疫学 免疫学 免疫学
背景情况:
- 在喘中,呼吸道重塑涉及呼吸道光滑肌细胞 (ASMC) 现型调节,以促进增殖和合成.
- STIM1和Orai1,对于存储运行的进入 (SOCE) 来说至关重要,涉及到增强ASMC的扩散和迁移.
研究的目的:
- 调查STIM1/Orai1介导的SOCE在ASMC表型转变中的作用.
- 确定SOCE对喘中细胞外基质 (ECM) 沉积的影响.
主要方法:
- 用PDGF-BB治疗ASMC,以诱导增殖/合成表型,并使用SOCE抑制剂 (SKF-96365,RO2959).
- 评估了ASMC增殖,收缩性蛋白质表达,炎症性细胞因子分泌和ECM成分 (原I,纤维素,MMPs) 的产生.
- 在体内研究评估了SOCE抑制剂对喘小鼠模型ECM沉积的影响.
主要成果:
- 现型切换的ASMCs显示STIM1,Orai1和SOCE活动升高.
- SOCE 抑制剂降低了ASMC的扩散,炎症性细胞因子分泌,并恢复了收缩性蛋白质水平.
- 抑制SOCE降低了ECM成分 (原I,纤维素) 和矩阵金属蛋白酶 (MMPs) 在体外和体内.
结论:
- 在STIM1/Orai1中介的SOCE显著推动ASMC表型调制和过度ECM沉积.
- 向STIM1/Orai1介导的SOCE呈现了一种潜在的治疗策略,用于缓解喘中的呼吸道重塑.
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