ArticleThe Journal of physiology2012
Rescue of epithelial HCO3- secretion in murine intestine by apical membrane expression of the cystic fibrosis transmembrane conductance regulator mutant F508del.
Article in The Journal of physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Distinct Roles of SLC26A3 and CFTR in Surface pH Regulation and Bicarbonate Secretion in Human Intestinal Epithelium.Acta physiologica (Oxford, England) · 2026Article
- DR5 Governs Compound Exocytosis in Colonic Goblet Cells via TATA-Box Binding Protein-Dependent Bestrophin-2 Transcriptional Regulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Bicarbonate secretion and acid/base sensing by the intestine.Pflugers Archiv : European journal of physiology · 2024Review
- Inhibition of mucus secretion by niclosamide and benzbromarone in airways and intestine.Scientific reports · 2024Article
- The Anion Channel TMEM16a/Ano1 Modulates CFTR Activity, but Does Not Function as an Apical Anion Channel in Colonic Epithelium from Cystic Fibrosis Patients and Healthy Individuals.International journal of molecular sciences · 2023Article
- The NHE3 Inhibitor Tenapanor Prevents Intestinal Obstructions in CFTR-Deleted Mice.International journal of molecular sciences · 2022Article
- Alterations of mucosa-attached microbiome and epithelial cell numbers in the cystic fibrosis small intestine with implications for intestinal disease.Scientific reports · 2022Article
- Advances in CaExperimental and therapeutic medicine · 2020Review
- Impaired Intestinal Farnesoid X Receptor Signaling in Cystic Fibrosis Mice.Cellular and molecular gastroenterology and hepatology · 2020Article
- cAMP Stimulates SLC26A3 Activity in Human Colon by a CFTR-Dependent Mechanism That Does Not Require CFTR Activity.Cellular and molecular gastroenterology and hepatology · 2019Article
- WNK1 and p38-MAPK distribution in ionocytes and accessory cells of euryhaline teleost fish implies ionoregulatory function.Biology open · 2017Article
- Defective small intestinal anion secretion, dipeptide absorption, and intestinal failure in suckling NBCe1-deficient mice.Pflugers Archiv : European journal of physiology · 2016Article
- Genetic Inhibition Of The Ubiquitin Ligase Rnf5 Attenuates Phenotypes Associated To F508del Cystic Fibrosis Mutation.Scientific reports · 2015Article
- Loss of Slc26a9 anion transporter alters intestinal electrolyte and HCO3(-) transport and reduces survival in CFTR-deficient mice.Pflugers Archiv : European journal of physiology · 2015Article
- Molecular transport machinery involved in orchestrating luminal acid-induced duodenal bicarbonate secretion in vivo.The Journal of physiology · 2013Article
- Normal mucus formation requires cAMP-dependent HCO3- secretion and Ca2+-mediated mucin exocytosis.The Journal of physiology · 2013Article
- Essential role of the electroneutral Na+-HCO3- cotransporter NBCn1 in murine duodenal acid-base balance and colonic mucus layer build-up in vivo.The Journal of physiology · 2013Article
- Multicenter intestinal current measurements in rectal biopsies from CF and non-CF subjects to monitor CFTR function.PloS one · 2013Article
- Rescue of murine F508del CFTR activity in native intestine by low temperature and proteasome inhibitors.PloS one · 2012Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study investigated whether expression of the common cystic fibrosis transmembrane conductance regulator (CFTR) mutant F508del in the apical membrane of enterocytes confers increased bicarbonate secretory capacity on the intestinal epithelium of F508del mutant mice compared to that of CFTR knockout (KO) mice. CFTR KO mice, F508del mutant mice (F508del) and wild-type (WT) littermates were bred on the FVB/N background. F508del isolated brush border membrane (BBM) contained approximately 5-10% fully glycosylated band C protein compared to WT BBM. Similarly, the forskolin (FSK)-induced, CFTR-dependent short-circuit current (I(sc)) of F508del mucosa was approximately 5-10% of WT, whereas the HCO(3)(-) secretory response ( ) was almost half that of WT in both duodenum and mid-colon studied in vitro and in vivo. While WT intestine retained full FSK-induced in the absence of luminal Cl(-), the markedly higher than I(sc) in F508del intestine was dependent on the presence of luminal Cl(-), and was blocked by CFTR inhibitors. The Ste20-related proline-alanine-rich kinases (SPAK/OSR1), which are downstream of the with-no-lysine (K) protein kinases (WNK), were rapidly phosphorylated by FSK in WT and F508del, but significantly more slowly in CFTR KO intestine. In conclusion, the data demonstrate that low levels of F508del membrane expression in the intestine of F508del mice significantly increased FSK-induced HCO(3)(-) secretion mediated by Cl(-)/HCO(3)(-) exchange. However, in WT mucosa FSK elicited strong SPAK/OSR1 phosphorylation and Cl(-)-independent HCO(3)(-) efflux. This suggests that therapeutic strategies which deliver F508del to the apical membrane have the potential to significantly enhance epithelial HCO(3)(-) secretion.
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