Nat Aging:SIRT3基因疗法缓解年龄相关肺纤维化

2021-02-16 haibei MedSci原创

最近,研究人员在Nature Aging杂志发文,表明了线粒体去乙酰化酶sirtuin 3 (SIRT3)在特发性肺纤维化的人类肺部和肺损伤的小鼠中下调。

纤维化疾病可以影响多个器官系统。在这些疾病中,一个一致的病理发现是激活的肌纤维细胞的积累、成熟的细胞外基质的沉积以及上皮细胞再生能力的受损。在大多数物种和人类的多种器官中,再生和纤维化是相互拮抗的。衰老是涉及包括肺部在内的各种器官系统的进行性纤维化疾病的一个风险因素。特发性肺纤维化是一种与年龄相关的肺部退行性疾病,其特点是持续存在抗凋亡的肌纤维细胞。

最近,研究人员在Nature Aging杂志发文,表明了线粒体去乙酰化酶sirtuin 3 (SIRT3)在特发性肺纤维化的人类肺部和肺损伤的小鼠中下调。通过气道递送过表达Sirt3 cDNA,可以缓解老年小鼠中纤维化的发生,这与成纤维细胞中FoxO3a的激活、Bcl2家族促凋亡成员的上调和凋亡敏感性的恢复有关。

虽然转化生长因子-β1降低了肺成纤维细胞中SIRT3和FOXO3A的水平,但涉及巨噬细胞分泌产物的细胞非自主效应是SIRT3介导的FOXO3A激活所必需的。

这些发现共同揭示了SIRT3在调节巨噬细胞功能中的新作用通过FOXO3A依赖性机制恢复成纤维细胞对凋亡的敏感性

 

原始出处:

Mohammad Rehan et al. Restoration of SIRT3 gene expression by airway delivery resolves age-associated persistent lung fibrosis in mice. Nature Aging (2021). 

 

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    2021-05-07 liye789132251
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    2021-02-16 carrotlyl

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