Cx26 regulates proliferation of repairing basal airway epithelial cells
S. Crespin, M. Bacchetta, J. Bou Saab, P. Tantilipikorn, J. Bellec, T. Dudez,T. Nguyen, B.R. Kwak,, J.S. Lacroix, S. Huang, L. Wiszniewski, M. Chanson
Laboratory of Clinical Investigation III, Geneva University Hospitals and University of Geneva, Switzerland,Mahidol University, Bangkok, Thailand,NSERM UMR 1064, CHU Nantes, ITUN, Nantes, France,Department of Pathology and Immunology, University of Geneva, Switzerland,Department of Internal Medicine – Cardiology, University of Geneva, Switzerland,Division of Otho-Rhino-Laryngology, Geneva University Hospitals, Geneva, Switzerland,Epithelix Sàrl, Plan-les-Ouates, Switzerland
The International Journal of Biochemistry & Cell Biology
The recovery of an intact epithelium following injury is critical for restoration of lung homeostasis, aprocess that may be altered in cystic fibrosis (CF). In response to injury, progenitor cells in the undamagedareas migrate, proliferate and re-differentiate to regenerate an intact airway epithelium. The mechanismsregulating this regenerative response are, however, not well understood. In a model of circular woundinjury of well-differentiated human airway epithelial cell (HAEC) cultures, we identified the gap junctionprotein Cx26 as an important regulator of cell proliferation. We report that induction of Cx26 in repairingHAECs is associated with cell proliferation. We also show that Cx26 is expressed in a population of CK14-positive basal-like cells. Cx26 silencing in immortalized cell lines using siRNA and in primary HAECs usinglentiviral-transduced shRNA enhanced Ki67-labeling index and Ki67 mRNA, indicating that Cx26 acts anegative regulator of HAEC proliferation. Cx26 silencing also markedly decreased the transcription ofKLF4 in immortalized HAECs. We further show that CF HAECs exhibited deregulated expression of KLF4,Ki67 and Cx26 as well enhanced rate of wound closure in the early response to injury. These results pointto an altered repair process of CF HAECs characterized by rapid but desynchronized initiation of HAECactivation and proliferation.This article is part of a Directed Issue entitled: Cystic fibrosis: From o-mics to cell biology, physiology,and therapeutic advances.