Function of KvLQT1 potassium channels in a mouse model of bleomycin-induced acute lung injury

被引:2
作者
Vega, Melissa Aubin [1 ,2 ]
Girault, Alban [1 ,2 ,3 ]
Meunier, Emilie [1 ,2 ]
Chebli, Jasmine [1 ,2 ]
Prive, Anik [1 ]
Robichaud, Annette [4 ]
Adam, Damien [1 ,2 ]
Brochiero, Emmanuelle [1 ,2 ]
机构
[1] Ctr Rech Ctr Hosp Univ Montreal CRCHUM, Montreal, PQ, Canada
[2] Univ Montreal, Dept Med, Montreal, PQ, Canada
[3] Lab Physiol Cellulaire & Mol LPCM UR UPJV 4667, Amiens, France
[4] SCIREQ Sci Resp Equipment Inc, Montreal, PQ, Canada
基金
加拿大自然科学与工程研究理事会; 加拿大健康研究院;
关键词
potassium channels; acute lung injury; animal model; pulmonary inflammation; respiratory function; injury and repair; alveolar-capillary barrier; RESPIRATORY-DISTRESS-SYNDROME; INFLAMMATORY CYTOKINES; K+ CHANNELS; PERSISTENT ELEVATION; FLUID CLEARANCE; PULMONARY-EDEMA; TRANSPORT; AIRWAY; TREK-1; CELLS;
D O I
10.3389/fphys.2024.1345488
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Acute respiratory distress syndrome (ARDS) is characterized by an exacerbated inflammatory response, severe damage to the alveolar-capillary barrier and a secondary infiltration of protein-rich fluid into the airspaces, ultimately leading to respiratory failure. Resolution of ARDS depends on the ability of the alveolar epithelium to reabsorb lung fluid through active transepithelial ion transport, to control the inflammatory response, and to restore a cohesive and functional epithelium through effective repair processes. Interestingly, several lines of evidence have demonstrated the important role of potassium (K+) channels in the regulation of epithelial repair processes. Furthermore, these channels have previously been shown to be involved in sodium/fluid absorption across alveolar epithelial cells, and we have recently demonstrated the contribution of KvLQT1 channels to the resolution of thiourea-induced pulmonary edema in vivo. The aim of our study was to investigate the role of the KCNQ1 pore-forming subunit of KvLQT1 channels in the outcome of ARDS parameters in a model of acute lung injury (ALI). We used a molecular approach with KvLQT1-KO mice challenged with bleomycin, a well-established ALI model that mimics the key features of the exudative phase of ARDS on day 7. Our data showed that KvLQT1 deletion exacerbated the negative outcome of bleomycin on lung function (resistance, elastance and compliance). An alteration in the profile of infiltrating immune cells was also observed in KvLQT1-KO mice while histological analysis showed less interstitial and/or alveolar inflammatory response induced by bleomycin in KvLQT1-KO mice. Finally, a reduced repair rate of KvLQT1-KO alveolar cells after injury was observed. This work highlights the complex contribution of KvLQT1 in the development and resolution of ARDS parameters in a model of ALI.
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页数:18
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共 72 条
  • [1] CFTR rescue with VX-809 and VX-770 favors the repair of primary airway epithelial cell cultures from patients with class II mutations in the presence of Pseudomonas aeruginosa exoproducts
    Adam, Damien
    Bilodeau, Claudia
    Sognigbe, Laura
    Maille, Emilie
    Ruffin, Manon
    Brochiero, Emmanuelle
    [J]. JOURNAL OF CYSTIC FIBROSIS, 2018, 17 (06) : 705 - 714
  • [2] K+ channels regulate ENaC expression via changes in promoter activity and control fluid clearance in alveolar epithelial cells
    Bardou, Olivier
    Prive, Anik
    Migneault, Francis
    Roy-Camille, Karl
    Dagenais, Andre
    Berthiaume, Yves
    Brochiero, Emmanuelle
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2012, 1818 (07): : 1682 - 1690
  • [3] Molecular diversity and function of K+ channels in airway and alveolar epithelial cells
    Bardou, Olivier
    Trinh, Nguyen Thu Ngan
    Brochiero, Emmanuelle
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2009, 296 (02) : L145 - L155
  • [4] Type 2 alveolar cells are stem cells in adult lung
    Barkauskas, Christina E.
    Cronce, Michael J.
    Rackley, Craig R.
    Bowie, Emily J.
    Keene, Douglas R.
    Stripp, Barry R.
    Randell, Scott H.
    Noble, Paul W.
    Hogan, Brigid L. M.
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (07) : 3025 - 3036
  • [5] SIGNIFICANCE OF ACTIVE ION-TRANSPORT IN TRANSALVEOLAR WATER-ABSORPTION - A STUDY ON ISOLATED RAT LUNG
    BASSET, G
    CRONE, C
    SAUMON, G
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1987, 384 : 311 - 324
  • [6] Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries
    Bellani, Giacomo
    Laffey, John G.
    Pham, Tai
    Fan, Eddy
    Brochard, Laurent
    Esteban, Andres
    Gattinoni, Luciano
    van Haren, Frank
    Larsson, Anders
    McAuley, Daniel F.
    Ranieri, Marco
    Rubenfeld, Gordon
    Thompson, B. Taylor
    Wrigge, Hermann
    Slutsky, Arthur S.
    Pesenti, Antonio
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2016, 315 (08): : 788 - 800
  • [7] Treatment of adult respiratory distress syndrome: plea for rescue therapy of the alveolar epithelium
    Berthiaume, Y
    Lesur, O
    Dagenais, A
    [J]. THORAX, 1999, 54 (02) : 150 - 160
  • [8] Enhanced insulin sensitivity of gene-targeted mice lacking functional KCNQ1
    Boini, Krishna M.
    Graf, Dirk
    Hennige, Anita M.
    Koka, Saisudha
    Kempe, Daniela S.
    Wang, Kan
    Ackermann, Teresa F.
    Foeller, Michael
    Vallon, Volker
    Pfeifer, Karl
    Schleicher, Erwin
    Ullrich, Susanne
    Haering, Hans-Ulrich
    Haeussinger, Dieter
    Lang, Florian
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2009, 296 (06) : R1695 - R1701
  • [9] Acute Respiratory Distress Syndrome 2022 1 Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes
    Bos, Lieuwe D. J.
    Ware, Lorraine B.
    [J]. LANCET, 2022, 400 (10358) : 1145 - 1156
  • [10] Pharmacotherapy for Prevention and Treatment of Acute Respiratory Distress Syndrome Current and Experimental Approaches
    Bosma, Karen J.
    Taneja, Ravi
    Lewis, James F.
    [J]. DRUGS, 2010, 70 (10) : 1255 - 1282