Autophagy in airway diseases: a new frontier in human asthma?
Autophagy in airway diseases: a new frontier in human asthma?
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作者：
Zeki AA;Yeganeh B;Kenyon NJ;Post M;Ghavami S
自噬(自噬)是参与生理和病理亚细胞过程的一种基本细胞命运途径，它的研究为不断寻找治疗人类哮喘的新方法开辟了一个新的前沿。哮喘是一种具有不同疾病表型的复杂综合征。自噬在细胞生理学、能量代谢、细胞存活等方面发挥着重要作用。自噬的特点是形成双膜自噬自噬小体，这一过程在哮喘的呼吸道上皮细胞和间充质细胞中可操作。已经观察到自噬基因和哮喘之间的遗传关联，包括ATG5的单核苷酸多态，它与肺功能降低相关。在哮喘中重要的免疫机制，如Th2细胞和嗜酸性粒细胞，也表现为自噬。最后，我们讨论了自噬在哮喘气道重塑中细胞外基质沉积和纤维化中的作用，这是一个仍然没有有效治疗的病理过程，并讨论了潜在的药物抑制剂。最后，我们就自噬如何直接参与呼吸道纤维化提出了两个相反但看似合理的假说。
The study of autophagy (‘self-eating’), a fundamental cell fate pathway involved in physiological and pathological subcellular processes, opens a new frontier in the continuous search for novel therapies for human asthma. Asthma is a complex syndrome with different disease phenotypes. Autophagy plays a central role in cell physiology, energy and metabolism, and cell survival. Autophagy’s hallmark is the formation of double-membrane autophagic autophagosomes, and this process is operational in airway epithelial and mesenchymal cells in asthma. Genetic associations between autophagy genes and asthma have been observed including single nucleotide polymorphisms in Atg5 which correlate with reduced lung function. Immune mechanisms important in asthma such as Th2 cells and eosinophils also manifest autophagy. Lastly, we address the role of autophagy in extracellular matrix deposition and fibrosis in asthmatic airways remodeling, a pathologic process still without effective therapy, and discuss potential pharmacologic inhibitors. We end by offering two opposing but plausible hypotheses as to how autophagy may be directly involved in airway fibrosis.