肺健康和疾病中的水通道蛋白：新兴作用、调控和临床意义,Respiratory Medicine

水通道蛋白 (AQP) 又名水通道是一系列在各种器官系统中表达的保守跨膜蛋白（~30 kDa 单体）。在人体的 13 种 AQP（AQP0 到 AQP12）中，有四种（AQP 1、3、4 和 5）在呼吸系统中表达。这些通道通常已知用于介导跨细胞流体运动。某些 AQP（aquaglyceroporins）具有运输甘油和其他潜在溶质的能力。越来越多的文献揭示了 AQPs 在细胞增殖和迁移、气体渗透、信号增强等方面的非常规作用。 最初的基因敲除研究确定了肺 AQPs，特别是 AQP5 在维持体内平衡，通过介导粘膜下腺体的液体分泌到气道表面液体 (ASL) 衬里。随后的研究强调了 AQPs，特别是 AQP1 和 AQP5 在肺病理生理学和疾病中的功能意义，包括但不限于慢性和急性肺损伤、慢性阻塞性肺病 (COPD)、其他炎症性肺病和肺癌。AQP1 已被建议作为恶性间皮瘤的潜在预后标志物。最近的努力旨在利用 AQP 作为诊断、预防、干预和/或治疗各种肺部疾病的目标。关于调控途径和定向机制研究的新兴信息被假定为揭示这些临床意义的新策略。未来的考虑应侧重于开发 AQP 抑制剂、阻滞剂和调节剂以满足治疗需求，

"点击查看英文标题和摘要"

Aquaporins (AQPs) aka water channels are a family of conserved transmembrane proteins (~30 kDa monomers) expressed in various organ systems. Of the 13 AQPs (AQP0 through AQP12) in the human body, four (AQPs 1, 3, 4, and 5) are expressed in the respiratory system. These channels are conventionally known for mediating transcellular fluid movements. Certain AQPs (aquaglyceroporins) have the capability to transport glycerol and potentially other solutes. There is an emerging body of literature unveiling the non-conventional roles of AQPs such as in cell proliferation and migration, gas permeation, signal potentiation, etc. Initial gene knock-out studies established a physiological role for lung AQPs, particularly AQP5, in maintaining homeostasis, by mediating fluid secretion from submucosal glands onto the airway surface liquid (ASL) lining. Subsequent studies have highlighted the functional significance of AQPs, particularly AQP1 and AQP5 in lung pathophysiology and diseases, including but not limited to chronic and acute lung injury, chronic obstructive pulmonary disease (COPD), other inflammatory lung conditions, and lung cancer. AQP1 has been suggested as a potential prognostic marker for malignant mesothelioma. Recent efforts are directed toward exploiting AQPs as targets for diagnosis, prevention, intervention, and/or treatment of various lung conditions. Emerging information on regulatory pathways and directed mechanistic research are posited to unravel novel strategies for these clinical implications. Future considerations should focus on development of AQP inhibitors, blockers, and modulators for therapeutic needs, and better understanding the role of lung-specific AQPs in inter-individual susceptibility to chronic lung diseases such as COPD and cancer.