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Article: Loss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epithelia

TitleLoss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epithelia
Authors
KeywordsHUMDISEASE
Issue Date2010
PublisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/cell
Citation
Cell, 2010, v. 143 n. 6, p. 911-923 How to Cite?
AbstractDefective transepithelial electrolyte transport is thought to initiate cystic fibrosis (CF) lung disease. Yet, how loss of CFTR affects electrolyte transport remains uncertain. CFTR -/- pigs spontaneously develop lung disease resembling human CF. At birth, their airways exhibit a bacterial host defense defect, but are not inflamed. Therefore, we studied ion transport in newborn nasal and tracheal/bronchial epithelia in tissues, cultures, and in vivo. CFTR -/- epithelia showed markedly reduced Cl - and HCO 3 - transport. However, in contrast to a widely held view, lack of CFTR did not increase transepithelial Na + or liquid absorption or reduce periciliary liquid depth. Like human CF, CFTR -/- pigs showed increased amiloride-sensitive voltage and current, but lack of apical Cl - conductance caused the change, not increased Na + transport. These results indicate that CFTR provides the predominant transcellular pathway for Cl - and HCO 3 - in porcine airway epithelia, and reduced anion permeability may initiate CF airway disease. © 2010 Elsevier Inc.
Persistent Identifierhttp://hdl.handle.net/10722/137013
ISSN
2015 Impact Factor: 28.71
2015 SCImago Journal Rankings: 28.188
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Heart Lung and Blood InstituteHL51670
HL091842
HL097622
National Institute of Diabetes and Digestive and Kidney DiseasesDK54759
Cystic Fibrosis Foundation
National Institute of Allergy and Infectious DiseasesAI076671
Funding Information:

We thank Lisaurie Lopez Rivera, Paula Ludwig, Theresa Mayhew, Peter Taft, Jingyang Zhang, and Yuping Zhang for excellent assistance. We thank Drs. John B Stokes and Peter M Snyder for helpful discussions. GlyH-101 was a generous gift from the Cystic Fibrosis Foundation Therapeutics and R. Bridges. This work was supported by the National Heart Lung and Blood Institute (grants HL51670, HL091842, and HL097622), the National Institute of Diabetes and Digestive and Kidney Diseases (grant DK54759), and the Cystic Fibrosis Foundation. D.A.S. is a Parker B. Francis Fellow and was supported by the National Institute of Allergy and Infectious Diseases (grant AI076671). M.J.W. is an Investigator of the HHMI. M.J.W. was a cofounder of Exemplar Genetics, a company that is licensing materials and technology related to this work.

References

 

DC FieldValueLanguage
dc.contributor.authorChen, JHen_HK
dc.contributor.authorStoltz, DAen_HK
dc.contributor.authorKarp, PHen_HK
dc.contributor.authorErnst, SEen_HK
dc.contributor.authorPezzulo, AAen_HK
dc.contributor.authorMoninger, TOen_HK
dc.contributor.authorRector, MVen_HK
dc.contributor.authorReznikov, LRen_HK
dc.contributor.authorLaunspach, JLen_HK
dc.contributor.authorChaloner, Ken_HK
dc.contributor.authorZabner, Jen_HK
dc.contributor.authorWelsh, MJen_HK
dc.date.accessioned2011-07-29T02:14:17Z-
dc.date.available2011-07-29T02:14:17Z-
dc.date.issued2010en_HK
dc.identifier.citationCell, 2010, v. 143 n. 6, p. 911-923en_HK
dc.identifier.issn0092-8674en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137013-
dc.description.abstractDefective transepithelial electrolyte transport is thought to initiate cystic fibrosis (CF) lung disease. Yet, how loss of CFTR affects electrolyte transport remains uncertain. CFTR -/- pigs spontaneously develop lung disease resembling human CF. At birth, their airways exhibit a bacterial host defense defect, but are not inflamed. Therefore, we studied ion transport in newborn nasal and tracheal/bronchial epithelia in tissues, cultures, and in vivo. CFTR -/- epithelia showed markedly reduced Cl - and HCO 3 - transport. However, in contrast to a widely held view, lack of CFTR did not increase transepithelial Na + or liquid absorption or reduce periciliary liquid depth. Like human CF, CFTR -/- pigs showed increased amiloride-sensitive voltage and current, but lack of apical Cl - conductance caused the change, not increased Na + transport. These results indicate that CFTR provides the predominant transcellular pathway for Cl - and HCO 3 - in porcine airway epithelia, and reduced anion permeability may initiate CF airway disease. © 2010 Elsevier Inc.en_HK
dc.languageengen_US
dc.publisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/cellen_HK
dc.relation.ispartofCellen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectHUMDISEASEen_HK
dc.titleLoss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epitheliaen_HK
dc.typeArticleen_HK
dc.identifier.emailChen, JH: jhlchen@hku.hken_HK
dc.identifier.authorityChen, JH=rp01518en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1016/j.cell.2010.11.029en_HK
dc.identifier.pmid21145458-
dc.identifier.pmcidPMC3057187-
dc.identifier.scopuseid_2-s2.0-78649915334en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78649915334&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume143en_HK
dc.identifier.issue6en_HK
dc.identifier.spage911en_HK
dc.identifier.epage923en_HK
dc.identifier.isiWOS:000285182600009-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10007064957-
dc.identifier.scopusauthoridChen, JH=7501878156en_HK
dc.identifier.scopusauthoridStoltz, DA=35273807000en_HK
dc.identifier.scopusauthoridKarp, PH=7006431484en_HK
dc.identifier.scopusauthoridErnst, SE=36706048700en_HK
dc.identifier.scopusauthoridPezzulo, AA=9234179500en_HK
dc.identifier.scopusauthoridMoninger, TO=6601992546en_HK
dc.identifier.scopusauthoridRector, MV=36626398000en_HK
dc.identifier.scopusauthoridReznikov, LR=36725696000en_HK
dc.identifier.scopusauthoridLaunspach, JL=36128673000en_HK
dc.identifier.scopusauthoridChaloner, K=36010499900en_HK
dc.identifier.scopusauthoridZabner, J=7005928925en_HK
dc.identifier.scopusauthoridWelsh, MJ=35447946600en_HK
dc.identifier.citeulike8449394-

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