The Emerging Importance of Autophagy in Pulmonary Diseases
The Emerging Importance of Autophagy in Pulmonary Diseases
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DOI：
10.1378/chest.12-0809
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发表时间：
2012-11-01
期刊：
影响因子：
9.6
通讯作者：
Choi, Augustine M. K.
中科院分区：
文献类型：
--
作者：
Mizumura, Kenji;Cloonan, Suzanne M.;Choi, Augustine M. K.
重要的细胞过程，如炎症、凋亡、分化和增殖，在人类疾病的发病机制中起着关键作用。在过去的十年中，一种名为“自噬”的新兴过程引起了生物医学研究和临床医学的强烈兴趣。自噬是一种受调节的细胞途径，通过溶酶体依赖的加工来周转生物体和蛋白质。虽然自噬曾被认为是一种整体降解事件，但研究表明，自噬选择性地降解特定蛋白质、细胞器和入侵细菌，这一过程被称为“选择性自噬”。越来越清楚的是，自噬与包括肺部疾病在内的临床疾病直接相关。本文概述了自噬过程的主要组成部分，并讨论了自噬和自噬蛋白在COPD、α(1)-抗胰蛋白酶缺乏症、肺动脉高压、急性肺损伤、囊性纤维化、呼吸道感染和败血症等肺部疾病中的重要性。最后，我们研究了肺自噬的双重性质，它具有保护和有害的作用，导致适应性和不适应反应，以及这种双重性对设计基于自噬的肺部疾病诊断和治疗靶点提出的挑战。胸部2012;145 (5): 1289 - 1299
Important cellular processes such as inflammation, apoptosis, differentiation, and proliferation confer critical roles in the pathogenesis of human diseases. In the past decade, an emerging process named "autophagy" has generated intense interest in both biomedical research and clinical medicine. Autophagy is a regulated cellular pathway for the turnover of organdies and proteins by lysosomal-dependent processing. Although autophagy was once considered a bulk degradation event, research shows that autophagy selectively degrades specific proteins, organelles, and invading bacteria, a process termed "selective autophagy." It is increasingly clear that autophagy is directly relevant to clinical disease, including pulmonary disease. This review outlines the principal components of the autophagic process and discusses the importance of autophagy and autophagic proteins in pulmonary diseases from COPD, alpha(1)-antitrypsin deficiency, pulmonary hypertension, acute lung injury, and cystic fibrosis to respiratory infection and sepsis. Finally, we examine the dual nature of autophagy in the lung, which has both protective and deleterious effects resulting from adaptive and maladaptive responses, and the challenge this duality poses for designing autophagy-based diagnostic and therapeutic targets in lung disease. CHEST 2012; 145(5):1289-1299