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

Our plain-English summary of Aquaporins in lung health and disease: Emerging roles, regulation, and clinical implications, by E. Yadav, N. Yadav, A. Hus, et al (Respiratory Medicine, 2020).

The study

• Authors: E. Yadav, N. Yadav, A. Hus, J.S. Yadav
• Journal: Respiratory Medicine
• Published: 2020;174:106193
• Type of article: Review
• Cited by: 64 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

Copyright © 2020 Elsevier Ltd. All rights reserved.

In plain English

This is a review article. The authors summarized published research on aquaporins, proteins that act as water channels in cell membranes, in the lungs and airways. They reported that four of the 13 human aquaporins (AQP1, AQP3, AQP4 and AQP5) are expressed in the respiratory system. They reviewed animal, cell and human studies on the roles of these proteins in lung injury, fibrosis, asthma, COPD and lung cancer. The review did not present new data of its own. One summarized study used a sheep lung model exposed to fluoro-edenite fibers, which the review describes as amphibole asbestos-like fibers, and the review's table lists decreased AQP1 in that model. Other summarized studies found AQP1 overexpressed in pleural mesothelioma and in epithelioid mesothelioma. One reported AQP1 overexpression to be an independent prognostic factor favoring survival in pleural mesothelioma. The authors concluded that AQP1 has been suggested as a potential prognostic marker in malignant mesothelioma. They noted that progress toward aquaporin-based treatments has been slow.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published studies (animal models, cell lines and human tissue studies) on aquaporins in lung health and disease
• Who was studied: No study population of its own. The review covers published research on the four aquaporins expressed in the human respiratory system (AQP1, AQP3, AQP4 and AQP5).
• Exposure: No single exposure. Among many conditions, the review covers studies of lung infections and environmental exposures, including silica, asbestos, irradiation and sulfur dioxide, and one sheep lung model exposed to fluoro-edenite fibers described as asbestos-like.
• Main results:
  • The review's table lists decreased AQP1 in a sheep lung model exposed to fluoro-edenite fibers (spelled 'fluoroadenite' in the table). The table describes these as amphibole asbestos-like fibers that cause chronic inflammation and carcinogenesis in lung tissue. This is a finding of a cited study (reference 78), not of this review.
  • The review reported that studies of various lung exposure and infection models (summarized in its Table 3) showed decreased lung AQP1 and/or AQP5. Chronic low-oxygen exposure was the exception: it showed increased AQP1.
  • A cited study (reference 114) reported that overexpression of AQP1 was an independent prognostic factor, favoring survival, in pleural mesothelioma.
  • A cited study of 92 lung biopsies (reference 107) found AQP1 overexpressed in primary lung adenocarcinomas and in pleural mesotheliomas.
  • Cited gene expression data mining on pleural malignant mesothelioma cases (reference 115) found AQP1 overexpressed in epithelioid mesothelioma. Patients with a deleted CDKN2A gene showed decreased AQP1 expression.
  • A cited study using immunohistochemical labeling of human lung tissue from 100 malignant mesothelioma cases (reference 116) emphasized the usefulness of AQP1 as a prognostic marker.
  • Cited chemical inhibitor experiments in a malignant mesothelioma model showed a role of AQP1 in cell adhesion, migration and sphere formation. Another cited study showed a role in vasculogenic mimicry, especially under low-oxygen conditions.
• The authors' conclusion: The authors concluded that there is accumulating evidence for roles of aquaporins, especially AQP1 and AQP5, in lung diseases. They stated that AQP1 has been suggested as a potential prognostic marker in pulmonary malignant mesothelioma. They called for more directed research on the clinical relevance of specific aquaporins, their regulation and their genetic variants.
• Limitations the authors state:
  • The authors stated that it is too early to say whether the non-water-transport functions of aquaporins explain their role in lung remodeling and repair.
  • The authors stated that progress in developing aquaporin-based treatments has been slow.
  • The authors noted that the knockout mouse studies cannot exclude compensatory mechanisms, which leaves the role of aquaporins open.
  • The authors noted that little has been achieved in identifying functionally relevant aquaporin genetic variants.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: COPD, Lung Cancer, Mesothelioma.

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