| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Alcolado, Nicole G. Conrad, Dustin J. Poroca, Diogo Li, Mansong Alshafie, Walaa Chappe, Frederic G. Pelis, Ryan M. Anini, Younes Xu, Zhaolin Hamidi, Sayyed Said, Sami I. Chappe, Valerie M. |
| Description |
Author Affiliation: Alcolado NG ( Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada); Conrad DJ ( Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada); Poroca D ( Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada); Li M ( Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada); Alshafie W ( Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada); Chappe FG ( Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada); Pelis RM ( Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada); Anini Y ( Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada); Xu Z ( Department of Pathology, Dalhousie University and QE II Health Sciences Centre, Halifax, Nova Scotia, Canada); Hamidi S ( Department of Medicine and Pulmonary Critical Care, Stony Brook University, Stony Brook, New York.); Said SI ( Department of Medicine and Pulmonary Critical Care, Stony Brook University, Stony Brook, New York.); Chappe VM ( Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada) |
| Abstract |
Vasoactive intestinal peptide (VIP), a neuropeptide, controls multiple functions in exocrine tissues, including inflammation, and relaxation of airway and vascular smooth muscles, and regulates CFTR-dependent secretion, which contributes to mucus hydration and local innate defense of the lung. We had previously reported that VIP stimulates the VPAC1 receptor, PKCϵ signaling cascade, and increases CFTR stability and function at the apical membrane of airway epithelial cells by reducing its internalization rate. Moreover, prolonged VIP stimulation corrects the molecular defects associated with F508del, the most common CFTR mutation responsible for the genetic disease cystic fibrosis. In the present study, we have examined the impact of the absence of VIP on CFTR maturation, cellular localization, and function in vivo using VIP knockout mice. We have conducted pathological assessments and detected signs of lung and intestinal disease. Immunodetection methods have shown that the absence of VIP results in CFTR intracellular retention despite normal expression and maturation levels. A subsequent loss of CFTR-dependent chloride current was measured in functional assays with Ussing chamber analysis of the small intestine ex vivo, creating a cystic fibrosis-like condition. Interestingly, intraperitoneal administration of VIP corrected tissue abnormalities, close to the wild-type phenotype, as well as associated defects in the vital CFTR protein. The results show in vivo a primary role for VIP chronic exposure in CFTR membrane stability and function and confirm in vitro data. |
| File Format |
HTM / HTML |
| ISSN |
03636143 |
| e-ISSN |
15221563 |
| DOI |
10.1152/ajpcell.00293.2013 |
| Journal |
American Journal of Physiology - Cell Physiology |
| Issue Number |
2 |
| Volume Number |
307 |
| Language |
English |
| Publisher |
American Physiological Society |
| Publisher Date |
2014-07-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Discipline Cell Biology Cystic Fibrosis Transmembrane Conductance Regulator Metabolism Epithelial Cells Physiology Vasoactive Intestinal Peptide Animals Genetics Gene Expression Regulation Intestine, Small Pathology Lung Mice Mice, Knockout Respiratory Mucosa Cytology Trachea Research Support, Non-u.s. Gov't |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cell Biology Physiology |
