Senescent AECⅡ and the implication for idiopathic pulmonary fibrosis treatment.
Senescent AECⅡ and the implication for idiopathic pulmonary fibrosis treatment.
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衰老AECⅨ及其对特发性肺纤维化治疗的意义
DOI：
10.3389/fphar.2022.1059434
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发表时间：
2022
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
特发性肺纤维化（IPF）是一种慢性致死性肺部疾病，治疗选择有限。IPF的发病率随年龄增长而增加，表明老龄化是IPF的主要风险因素。在衰老的标志中，细胞衰老是组织和器官衰老的原始驱动因素和主要病因，也是IPF进展的独立风险因素。本文就肺泡II型上皮细胞（AECIIs）的衰老进行综述，系统总结了IPF进展过程中AECIIs衰老的信号通路和生物学过程的异常变化及其意义。同时，我们客观地分析了目前针对消除衰老细胞或恢复活力的药物，如senolytics，senomorphics，自噬调节剂和干细胞治疗。最后，我们辩证地讨论了靶向衰老AECII治疗IPF的可行性和局限性。我们希望这一理解将为开发基于AECII的衰老方法以预防和缓解IPF提供新的见解。
Idiopathic pulmonary fibrosis (IPF) is a chronic and lethal lung disease with limited treatment options. The onset of IPF increases with age, indicating that aging is a major risk factor for IPF. Among the hallmarks of aging, cellular senescence is the primordial driver and primary etiological factor for tissue and organ aging, and an independent risk factor for the progression of IPF. In this review, we focus on the senescence of alveolar type II epithelial cells (AECIIs) and systematically summarize abnormal changes in signal pathways and biological process and implications of senescent AECIIs during IPF progression. Meanwhile, we objectively analyze current medications targeting the elimination of senescent cells or restoration of vitality such as senolytics, senomorphics, autophagy regulators, and stem cell therapy. Finally, we dialectically discuss the feasibility and limitation of targeting senescent AECIIs for IPF treatment. We hope that the understanding will provide new insights to the development of senescent AECII-based approaches for the prevention and mitigation of IPF.