通过减少circANKRD42-YAP1介导的机械刚性,hucMSCs的治疗可以预防肺纤维化
Haitong Zhang1, Qi Zhu2, Yunxia Ji1
1Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou 256603, China.
Aging
|June 19, 2023
概括
人类带介质干细胞 (hucMSCs) 在异常性肺纤维化 (IPF) 中降低肺组织刚性. 这种疗法针对circANKRD42-YAP1轴,提供了一种新的IPF治疗方法.
科学领域:
- 生物医学工程 生物医学工程
- 再生医学是一种再生医学.
- 肺部医学 肺部医学
背景情况:
- 异形性肺纤维化 (IPF) 是一种进展性肺病,其特征是增加组织硬性.
- 纤维环境的机械特性影响细胞行为和疾病进展.
- 人类带介质干细胞 (hucMSCs) 正在研究它们在IPF中的治疗潜力.
研究的目的:
- 通过hucMSCs确定IPF的新型治疗策略.
- 阐明hucMSCs疗法降低IPF机械性的机制.
- 探索circANKRD42-YAP1轴在IPF机械生物学中的作用.
主要方法:
- hucMSCs被标记,并使用肺功能分析,MicroCT和原子力显微镜评估它们的治疗效果.
- 在纤维化环境中分析了细胞机械连接和基因表达 (Myo1c,F-actin).
- 携带野生型和突变型circankrd42的腺病毒载体被用来研究circankrd42和miR-136-5p在调节YAP1表达中的作用.
主要成果:
- 一个刚性纤维化的环境促进了细胞质和细胞核之间的机械连接,提高了机械基因的调节.
- hucMSCs的治疗有效地阻断了力传递,并减少了肺组织的整体机械刚性.
- 机械研究表明,hucMSCs抑制circANKRD42生物发生,促进miR-136-5p与YAP1mRNA结合,从而减少YAP1核转位和下游机械基因表达.
结论:
- hucMSCs疗法通过通过circANKRD42-YAP1轴减少组织机械度来减轻IPF.
- 这项研究揭示了一种涉及IPF中circANKRD42和YAP1的新型机械感知机制.
- 这些发现表明,使用hucMSCs针对这个轴,为IPF治疗提供了一个有前途的治疗途径.
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