由线粒体DNA驱动的衰老相关的分泌表型促进支气管肺功能失调的发展
Yang Meng1,2, Hui Shi3, Hui Xu3
1Clinical Medical College, Yangzhou University, Yangzhou, People's Republic of China.
American journal of physiology. Cell physiology
|September 12, 2025
概括
支气管肺功能障碍 (BPD) 中的线粒体功能障碍导致DNA释放并激活cGAS-STING通路,驱动衰老相关的分泌表型 (SASP). 针对这种途径可以治疗BPD.
科学领域:
- 新生儿研究新生儿研究
- 细胞生物学 细胞生物学
- 肺部医学 肺部医学
背景情况:
- 支气管肺发育不良症 (BPD) 涉及早产婴儿的肺发育受损.
- 细胞衰老已知在成人肺部疾病中存在,但其在新生儿肺部疾病中的作用尚不清楚.
研究的目的:
- 研究老化相关分泌表型 (SASP) 在BPD中的作用和机制.
- 确定驱动BPD病变的关键分子通路.
主要方法:
- 在BPD模型中使用了向抑制剂治疗和救援策略.
- 在高氧化暴露后分析SASP因子水平 (例如IL-6,IL-1β).
- 利用共聚焦成像检查线粒体完整性和DNA泄漏.
主要成果:
- 过氧暴露显著增加了关键的SASP因素,使它们与BPD有关.
- 由mtDNA泄漏证明的线粒体功能障碍是BPD的关键驱动因素.
- 在VDAC1寡合化和cGAS-STING通路中介的mtDNA释放和SASP.
结论:
- 在BPD中出现了一种新的分子级联:VDAC1寡合化 -> mtDNA泄漏 -> cGAS-STING激活 -> SASP.
- 这一途径在氧化剂诱导的损伤过程中影响肺上皮细胞.
- 针对cGAS-STING通路提供了BPD的潜在治疗策略.
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