ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2009
Reduced NHE3-mediated Na+ absorption increases survival and decreases the incidence of intestinal obstructions in cystic fibrosis mice.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis.Nature communications · 2015Pooled it
- The NHE3 Inhibitor Tenapanor Prevents Intestinal Obstructions in CFTR-Deleted Mice.International journal of molecular sciences · 2022Article
- Further delineation of SLC9A3-related congenital sodium diarrhea.Molecular genetics & genomic medicine · 2022Article
- The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity.Frontiers in physiology · 2022Review
- The NaFrontiers in physiology · 2022Review
- Cystic Fibrosis Lung Disease Modifiers and Their Relevance in the New Era of Precision Medicine.Genes · 2021Review
- Novel Treatments from Inhibition of the Intestinal Sodium-Hydrogen Exchanger 3.International journal of nephrology and renovascular disease · 2021Review
- Pharmacological inhibition of sodium-proton-exchanger subtype 3-mediated sodium absorption in the gut reduces atrial fibrillation susceptibility in obese spontaneously hypertensive rats.International journal of cardiology. Heart & vasculature · 2020Article
- An inducible intestinal epithelial cell-specific NHE3 knockout mouse model mimicking congenital sodium diarrhea.Clinical science (London, England : 1979) · 2020Article
- Urinary concentrating defect in mice lacking Epac1 or Epac2.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- SLC9A3 Affects Vas Deferens Development and Associates with Taiwanese Congenital Bilateral Absence of the Vas Deferens.BioMed research international · 2019Article
- Linaclotide improves gastrointestinal transit in cystic fibrosis mice by inhibiting sodium/hydrogen exchanger 3.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Recent advances in developing therapeutics for cystic fibrosis.Human molecular genetics · 2018Review
- Article
- Renal tubular NHE3 is required in the maintenance of water and sodium chloride homeostasis.Kidney international · 2017Article
- Loss of SLC9A3 decreases CFTR protein and causes obstructed azoospermia in mice.PLoS genetics · 2017Article
- Novel developments in differentiating the role of renal and intestinal sodium hydrogen exchanger 3.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Review
- Intestinal brush-border Na+/H+ exchanger-3 drives H+-coupled iron absorption in the mouse.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Differential expression of pancreatic protein and chemosensing receptor mRNAs in NKCC1-null intestine.World journal of gastrointestinal pathophysiology · 2016Article
- Unraveling the complex genetic model for cystic fibrosis: pleiotropic effects of modifier genes on early cystic fibrosis-related morbidities.Human genetics · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
In cystic fibrosis, impaired secretion resulting from loss of activity of the cystic fibrosis transmembrane conductance regulator (CFTR) causes dehydration of intestinal contents and life-threatening obstructions. Conversely, impaired absorption resulting from loss of the NHE3 Na+/H+ exchanger causes increased fluidity of the intestinal contents and diarrhea. To test the hypothesis that reduced NHE3-mediated absorption could increase survival and prevent some of the intestinal pathologies of cystic fibrosis, Cftr/Nhe3 double heterozygous mice were mated and their offspring analyzed. Cftr-null mice lacking one or both copies of the NHE3 gene exhibited increased fluidity of their intestinal contents, which prevented the formation of obstructions and increased survival. Goblet cell hyperplasia was eliminated, but not the accumulation of Paneth cell granules or increased cell proliferation in the crypts. Microarray analysis of small intestine RNA from Cftr-null, NHE3-null, and double-null mice all revealed downregulation of genes involved in xenobiotic metabolism, including a cohort of genes involved in glutathione metabolism. Expression of energy metabolism genes was altered, but there were no changes in genes involved in inflammation. Total intracellular glutathione was increased in the jejunum of all of the mutants and the ratio of reduced to oxidized glutathione was reduced in Cftr-null mutants, indicating that CFTR deficiency affects intestinal glutathione metabolism. The data establish a major role for NHE3 in regulating the fluidity of the intestinal contents and show that reduced NHE3-mediated absorption reverses some of the intestinal pathologies of cystic fibrosis, thus suggesting that it may serve as a potential therapeutic target.
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