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Article Dans Une Revue American Journal of Physiology - Lung Cellular and Molecular Physiology Année : 2021

Phospholipase C controls chloride-dependent short-circuit current in human bronchial epithelial cells

Résumé

Chloride secretion by airway epithelial cells is primordial for water and ion homeostasis and airways surface prevention of infections. This secretion is impaired in several human diseases, including cystic fibrosis, a genetic pathology due to CFTR gene mutations leading to chloride channel defects. A potential therapeutic approach is aiming at increasing chloride secretion either by correcting the mutated CFTR itself or by stimulating non-CFTR chloride channels at the plasma membrane. Here, we studied the role of phospholipase C in regulating the transepithelial chloride secretion in human airway epithelial 16HBE14o- and CFBE cells over-expressing wild type (WT)- or F508del-CFTR. Western blot analysis shows expression of the three endogenous phospholipase C (PLC) isoforms, namely, PLCδ1, PLCγ1, and PLCβ3 in 16HBE14o- cells. In 16HBE14o- cells, we performed Ussing chamber experiments after silencing each of these PLC isoforms or using the PLC inhibitor U73122 or its inactive analogue U73343. Our results show the involvement of PLCβ3 and PLCγ1 in CFTR-dependent short-circuit current activated by forskolin, but not of PLCδ1. In CFBE-WT CFTR and corrected CFBE-F508del CFTR cells, PLCβ3 silencing also inhibits CFTR-dependent current activated by forskolin and UTP-activated calcium-dependent chloride channels (CaCC). Our study supports the importance of PLC in maintaining CFTR-dependent chloride secretion over time, getting maximal CFTR-dependent current and increasing CaCC activation in bronchial epithelial cells.
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Dates et versions

hal-04541620 , version 1 (10-04-2024)

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Chloé Grebert, Frédéric Becq, Clarisse Vandebrouck. Phospholipase C controls chloride-dependent short-circuit current in human bronchial epithelial cells. American Journal of Physiology - Lung Cellular and Molecular Physiology, 2021, 320 (2), pp.L205-L219. ⟨10.1152/ajplung.00437.2019⟩. ⟨hal-04541620⟩
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