通过染色体重塑因子CHD4,β1整蛋白信号传递控制了亡的过程
Zhiqi Sun1, Filippo M Cernilogar2, Helena Horvatic3
1Gene Center and Department of Biochemistry, Ludwig Maximilian University of Munich, Munich, Germany; Research Group Molecular Mechanisms of Inflammation, Max-Planck Institute of Biochemistry, Martinsried, Germany.
Cell reports
|October 26, 2023
概括
纤维细胞激活和纤维化炎症是由β1整合蛋白信号传递联系在一起. 这一途径通过一种涉及染色体基酶DNA结合蛋白4 (CHD4) 的新机制调节受体相互作用蛋白激酶3 (RIPK3) 的表达.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 纤维化涉及肌纤维细胞激活和过度的细胞外基质 (ECM) 沉积,通常与慢性炎症有关.
- 受体相互作用蛋白激酶3 (RIPK3) 是亡信号传递中的关键激酶,在纤维化中被上调,并有助于TNF介导的炎症.
研究的目的:
- 研究RIPK3在肝纤维化中的作用.
- 阐明β1整合素信号传导影响肌纤维细胞中RIPK3表达的机制.
- 描述染色体酶DNA结合蛋白4 (CHD4) 在调节RIPK3.3中的功能.
主要方法:
- 胆道结合诱导的小鼠肝纤维化模型.
- 纤维细胞中β1整体素的遗传性除.
- 在肌纤维细胞中RIPK3表达的分析.
- 染色体免疫沉和基因表达分析以研究CHD4功能.
主要成果:
- 肌纤维细胞被确定为肝纤维化中的主要RIPK3表达细胞.
- 基因切除β1整合素减少了ECM沉积和削弱了RIPK3的表达.
- 通过染色体重塑因子CHD4.4调节RIPK3的下调.
- CHD4抑制Ripk3表达独立于NuRD或CHAHP复合体,表明一种新的作用模式.
结论:
- β1整蛋白信号传递对于将纤维化过程与RIPK3驱动的炎症联系起来至关重要.
- CHD4在抑制Ripk3基因表达方面发挥了新的,局部特异性的作用,独立于已知的复合体.
- 这项研究揭示了一种新的机制,将ECM受体信号与纤维化中的炎症激酶调节联系起来.
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