Elsevier

Respiratory Medicine

Volume 174, November–December 2020, 106193
Respiratory Medicine

Review article
Aquaporins in lung health and disease: Emerging roles, regulation, and clinical implications

https://doi.org/10.1016/j.rmed.2020.106193Get rights and content
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Highlights

  • Both basic and clinical aspects of lung aquaporins (AQPs) covered.

  • Focus on emerging functional roles of AQPs in lung physiology and pathophysiology.

  • Regulatory pathways governing expression of lung AQPs summarized.

  • Highlights Potential of AQPs for diagnosis, prognosis, and intervention/treatment.

  • Expected to stimulate further studies on lung AQPs as druggable targets.

Abstract

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.

Keywords

Aquaporins
Lung pathophysiology
Regulation
Acute lung injury
Lung inflammation
Chronic obstructive pulmonary disease
Lung cancer

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