Effect of hypoxia on Cystic Fibrosis Transmembrane conductance Regulator channel corrected by Elexacaftor/Tezacaftor/Ivacaftor - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Medical Research Archives Année : 2024

Effect of hypoxia on Cystic Fibrosis Transmembrane conductance Regulator channel corrected by Elexacaftor/Tezacaftor/Ivacaftor

Résumé

The accumulation of mucus resulting from the obstruction of bronchi of cystic fibrosis (CF) patients, induces a reduction of the oxygen (O2) pressure and produces a hypoxic environment for the epithelial cells of the lungs. Our study aims to better characterize the impact of hypoxia on CFTR function in the pathophysiological context of cystic fibrosis. We used Human airway epithelial cells from two CF donors and human bronchial epithelial cell lines non-CF and CF, grown and expended in normoxia (21% O2) and then switched to hypoxia (1% O2) for 2 to 24 hours. Cells were treated by dimethyl sulfoxide or Elexacaftor/ Tezacaftor/Ivacaftor for 24 hours. We show that the peak of Hypoxia Inducible Factor 1α is reached in a range of 4 to 6 hours post-hypoxia induction. We also demonstrate that the global amount of ETI corrected F508del-CFTR is significantly decreased after 24 hours of hypoxia. A decreased ETI corrected F508del-CFTR activity was recorded by both patch-clamp and Ussing chamber recordings. Our results show that hypoxia, despite the effectiveness of Elexacaftor/ Tezacaftor/Ivacaftor correction, impacts the downstream effects of the F508del mutation, which suggests that oxygen availability in the lungs is a factor to take into account for the administration of Trikafta to patients.
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hal-04496971 , version 1 (13-03-2024)

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K. Pascarel, Jenny Colas, Thomas Carrez, Christine Barrault, Sandra Mirval, et al.. Effect of hypoxia on Cystic Fibrosis Transmembrane conductance Regulator channel corrected by Elexacaftor/Tezacaftor/Ivacaftor. Medical Research Archives, 2024, 12 (2), ⟨10.18103/mra.v12i2.4909⟩. ⟨hal-04496971⟩
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