转录因子MEOX1通过调节线粒和衰老来加速肺纤维化
Lijun Fang1, Linmao Lyu2, Hongyu Zhong3
1Department of Pulmonary and Critical Care Medicine, Laboratory of Basic Medical Sciences, Shandong University Qilu Hospital, Jinan, 250012, China.
European journal of pharmacology
|August 8, 2025
概括
梅基母体盒1 (MEOX1) 抗击剂通过改善线粒和减少纤维细胞衰老来保护肺纤维化. 这表明MEOX1是异常性肺纤维化的潜在治疗标.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 异形性肺纤维化 (IPF) 是一种进展性肺病,原因不明.
- 转化生长因子-β1 (TGF-β1) 通过诱导线粒细胞功能障碍和纤维细胞衰老来驱动IPF.
- 在肺纤维化和线粒细胞衰老中,梅森基姆本体盒1 (MEOX1) 的作用尚不清楚.
研究的目的:
- 调查MEOX1在肺纤维化和线粒细胞衰变的病变发生过程中的作用.
- 探索MEOX1作为IPF的潜在治疗点.
主要方法:
- 用RNA测序来识别TGF-β1治疗的肺纤维细胞和IPF组织中差异表达的基因.
- 在体内小鼠模型的肺纤维化由白素 (BLM) 诱导.
- 在小鼠中使用腺相关病毒 (AAV) -shMEOX1.1.shMEOX1进行纤维细胞特异性MEOX1敲击.
- 在人肺纤维细胞的体外研究.
主要成果:
- 纤维细胞特异性MEOX1敲击保护小鼠免受BLM诱导的肺纤维化,结缔组织生长因子 (CTGF) 表达和纤维细胞激活.
- MEOX1 knockdown 逆转了纤维化肺部的线粒细胞衰变缺陷和衰老.
- 在体外,MEOX1 knockdown 抑制了TGF-β1诱导的髓缺陷,CTGF表达,纤维细胞衰老和原蛋白生产.
- TGF-β1通过NOX4-ROS-Smad通路对MEOX1进行上调.
结论:
- 通过调节线粒消化和衰老,MEOX1 Knockdown可以改善肺纤维化.
- MEOX1是TGF-β1诱导的肺纤维细胞功能障碍的关键调解者.
- 向MEOX1可能为IPF和其他间歇性肺部疾病提供一种新的治疗策略.
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