Deleterious impact of hyperglycemia on cystic fibrosis airway ion transport and epithelial repair.
BACKGROUND
Cystic fibrosis (CF)-related diabetes (CFRD) is associated with faster pulmonary function decline. Thus, we evaluated the impact of hyperglycemia on airway epithelial repair and transepithelial ion transport, which are critical in maintaining lung integrity and function.


METHODS
Non-CF and CF airway epithelial cells were exposed to low (LG) or high (HG) glucose before ion current and wound repair rate measurements.


RESULTS
CFTR and K+ currents decreased after HG treatments. HG also reduced the wound healing rates of non-CF and CF cell monolayers. Although CFTR correction with VRT-325 accelerated the healing rates of CF cells monolayers under LG conditions, this improvement was significantly abrogated under HG conditions.


CONCLUSIONS
Our data highlights a deleterious impact of hyperglycemia on ion transport and epithelial repair functions, which could contribute to the deterioration in lung function in CFRD patients. HG may also interfere with the beneficial effects of CFTR rescue on airway epithelial repair.
Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), 900 rue Saint-Denis, Montréal, Québec H2X0A9, Canada; Département de médecine, Université de Montréal, CP6128, Succursale Centre-Ville, Montréal, Québec H3C3J7, Canada. Electronic address: claudia.bilodeau@umontreal.ca.
Claudia
C
Bilodeau
Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), 900 rue Saint-Denis, Montréal, Québec H2X0A9, Canada; Département de médecine, Université de Montréal, CP6128, Succursale Centre-Ville, Montréal, Québec H3C3J7, Canada. Electronic address: olivier.bardou@inserm.fr.
Olivier
O
Bardou
Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), 900 rue Saint-Denis, Montréal, Québec H2X0A9, Canada. Electronic address: emilie.maille.chum@ssss.gouv.qc.ca.
Émilie
É
Maillé
Département de médecine, Université de Montréal, CP6128, Succursale Centre-Ville, Montréal, Québec H3C3J7, Canada; Institut de recherches cliniques de Montréal (IRCM), 110 avenue des Pins Ouest, Montréal, Québec H2W1R7, Canada. Electronic address: yves.berthiaume@umontreal.ca.
Yves
Y
Berthiaume
Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), 900 rue Saint-Denis, Montréal, Québec H2X0A9, Canada; Département de médecine, Université de Montréal, CP6128, Succursale Centre-Ville, Montréal, Québec H3C3J7, Canada. Electronic address: emmanuelle.brochiero@umontreal.ca.
Emmanuelle
E
Brochiero
D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D062326:Re-Epithelialization / Q000187:drug effects / Q000502:physiology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D013549:Sweetening Agents / Q000378:metabolism / Q000494:pharmacology
D013549:Sweetening Agents; D005947:Glucose
Airways; CFTR; Cystic fibrosis; Diabetes; Epithelial repair; K(+) channels