p19Arf Exacerbates Cigarette Smoke-Induced Pulmonary Dysfunction
p19Arf Exacerbates Cigarette Smoke-Induced Pulmonary Dysfunction
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DOI：
10.3390/biom10030462
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发表时间：
2020-03-01
期刊：
影响因子：
5.5
通讯作者：
Sugimoto, Masataka
中科院分区：
文献类型：
--
作者：
Mikawa, Ryuta;Sato, Tadashi;Sugimoto, Masataka
衰老细胞在衰老或病理环境中积累在组织中。衰老细胞的半遗传或药理学靶向揭示了细胞衰老是衰老相关表型和疾病的许多方面的基础。我们以前报道过细胞衰老导致与衰老和疾病相关的肺功能障碍。我们在本文中报告说，消除Arf表达细胞可以改善香烟烟雾诱导的小鼠肺部病变。香烟烟雾诱导Ink4a和Arf在肺组织中的表达，伴随着肺组织顺应性和肺泡气隙的增加。在香烟烟雾暴露之前消除Arf表达细胞可以防止这些变化。此外，香烟烟雾提取物的施用导致肺功能障碍，其通过随后的衰老细胞消除而得到改善。总的来说，这些结果表明，衰老细胞是吸烟相关肺部疾病的潜在治疗靶点。
Senescent cells accumulate in tissues during aging or pathological settings. The semi-genetic or pharmacological targeting of senescent cells revealed that cellular senescence underlies many aspects of the aging-associated phenotype and diseases. We previously reported that cellular senescence contributes to aging- and disease-associated pulmonary dysfunction. We herein report that the elimination of Arf-expressing cells ameliorates cigarette smoke-induced lung pathologies in mice. Cigarette smoke induced the expression of Ink4a and Arf in lung tissue with concomitant increases in lung tissue compliance and alveolar airspace. The elimination of Arf-expressing cells prior to cigarette smoke exposure protected against these changes. Furthermore, the administration of cigarette smoke extract lead to pulmonary dysfunction, which was ameliorated by subsequent senescent cell elimination. Collectively, these results suggest that senescent cells are a potential therapeutic target for cigarette smoking-associated lung disease.