dc.contributor.author
Balázs, Anita
dc.contributor.author
Mall, Marcus A.
dc.date.accessioned
2019-04-10T07:32:57Z
dc.date.available
2019-04-10T07:32:57Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/24338
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-2110
dc.description.abstract
The solute carrier family 26, member 9 (SLC26A9) is an epithelial chloride channel that is expressed in several organs affected in patients with cystic fibrosis (CF) including the lungs, the pancreas, and the intestine. Emerging evidence suggests SLC26A9 as a modulator of wild-type and mutant CFTR function, and as a potential alternative target to circumvent the basic ion transport defect caused by deficient CFTR-mediated chloride transport in CF. In this review, we summarize in vitro studies that revealed multifaceted molecular and functional interactions between SLC26A9 and CFTR that may be implicated in normal transepithelial chloride secretion in health, as well as impaired chloride/fluid transport in CF. Further, we focus on recent genetic association studies and investigations utilizing genetically modified mouse models that identified SLC26A9 as a disease modifier and supported an important role of this alternative chloride channel in the pathophysiology of several organ manifestations in CF, as well as other chronic lung diseases such as asthma and non-CF bronchiectasis. Collectively, these findings and the overlapping endogenous expression with CFTR suggest SLC26A9 an attractive novel therapeutic target that may be exploited to restore epithelial chloride secretion in patients with CF irrespective of their CFTR genotype. In addition, pharmacological activation of SLC26A9 may help to augment the effect of CFTR modulator therapies in patients with CF carrying responsive mutations such as the most common disease-causing mutation F508del-CFTR. However, future research and development including the identification of compounds that activate SLC26A9-mediated chloride transport are needed to explore this alternative chloride channel as a therapeutic target in CF and potentially other muco-obstructive lung diseases.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
cystic fibrosis
en
dc.subject
epithelial ion transport
en
dc.subject
chloride channels
en
dc.subject
pharmacology
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Role of the SLC26A9 chloride channel as disease modifier and potential therapeutic target in cystic fibrosis
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
1112
dcterms.bibliographicCitation.doi
10.3389/fphar.2018.01112
dcterms.bibliographicCitation.journaltitle
Frontiers in Pharmacology
dcterms.bibliographicCitation.originalpublishername
Frontiers Media S.A.
dcterms.bibliographicCitation.volume
9
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
30327603
dcterms.isPartOf.issn
1663-9812