Cellular Senescence: Pathogenic Mechanisms in Lung Fibrosis.
Cellular Senescence: Pathogenic Mechanisms in Lung Fibrosis.
复制标题
细胞衰老：肺纤维化的致病机制。
DOI：
10.3390/ijms22126214
复制
发表时间：
2021-06-09
影响因子：
5.6
通讯作者：
Yao C
中科院分区：
文献类型：
--
作者：
Parimon T;Hohmann MS;Yao C
肺纤维化是一种慢性和致命的肺部疾病，严重影响全球老龄化人口。迄今为止，抗纤维化、免疫抑制和其他辅助治疗显示出有限的疗效。进一步了解肺纤维化的发病机制将为未来的治疗提供一条途径。由于老年组中纤维增生性肺病的发病率增加，细胞衰老在近几十年来获得了极大的兴趣。此外，包括适应不良的组织修复、再生减少和慢性炎症的细胞衰老的病理状态类似于进行性肺纤维化的关键特征。本文综述了细胞衰老的调控途径，并讨论了肺纤维化的关键细胞参与者，包括上皮细胞（肺泡2型细胞，基底细胞等），成纤维细胞和免疫细胞，它们的表型变化，以及这些细胞促成肺纤维化发病机制的细胞和分子机制。该领域的一些挑战包括建立适当的体内实验模型和鉴定衰老靶向信号分子和靶向衰老细胞的特异性疗法，统称为“衰老清除剂”或“衰老抑制剂”。
Pulmonary fibrosis is a chronic and fatal lung disease that significantly impacts the aging population globally. To date, anti-fibrotic, immunosuppressive, and other adjunct therapy demonstrate limited efficacies. Advancing our understanding of the pathogenic mechanisms of lung fibrosis will provide a future path for the cure. Cellular senescence has gained substantial interest in recent decades due to the increased incidence of fibroproliferative lung diseases in the older age group. Furthermore, the pathologic state of cellular senescence that includes maladaptive tissue repair, decreased regeneration, and chronic inflammation resembles key features of progressive lung fibrosis. This review describes regulatory pathways of cellular senescence and discusses the current knowledge on the senescence of critical cellular players of lung fibrosis, including epithelial cells (alveolar type 2 cells, basal cells, etc.), fibroblasts, and immune cells, their phenotypic changes, and the cellular and molecular mechanisms by which these cells contribute to the pathogenesis of pulmonary fibrosis. A few challenges in the field include establishing appropriate in vivo experimental models and identifying senescence-targeted signaling molecules and specific therapies to target senescent cells, known collectively as “senolytic” or “senotherapeutic” agents.
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影响因子：
4.4
作者：
Agrawal A;Sridharan A;Prakash S;Agrawal H
通讯作者：
Agrawal H
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
3.1
作者：
Choi WI;Dauti S;Kim HJ;Park SH;Park JS;Lee CW
通讯作者：
Lee CW
DOI：
10.1164/rccm.201905-1017oc
发表时间：
2020-03-01
影响因子：
24.7
作者：
Allen, Richard J.;Guillen-Guio, Beatriz;Wain, Louise, V
通讯作者：
Wain, Louise, V
影响因子：
82.9
作者：
Childs BG;Durik M;Baker DJ;van Deursen JM
通讯作者：
van Deursen JM