ArticleAmerican journal of physiology. Cell physiology2009
Tumor necrosis factor-{alpha} downregulates intestinal NHE8 expression by reducing basal promoter activity.
Article in American journal of physiology. Cell physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Sex and race differences in urinary Tumor Necrosis Factor-α (TNF-α) levels: Secondary analysis of the DASH-sodium trial.Journal of human hypertension · 2023Trial
- Vitamin D/VDR Signaling and Programmed Cell Death in Sepsis-Associated Organ Injury: Evidence from Sepsis and Related Disease Models.Journal of inflammation research · 2026Review
- Compromised NHE8 Expression Is Responsible for Vitamin D-Deficiency Induced Intestinal Barrier Dysfunction.Nutrients · 2023Article
- The Expression of NHE8 in Liver and Its Role in Carbon Tetrachloride-Induced Liver Injury.Gastro hep advances · 2023Article
- The Physiological Function and Potential Role of the Ubiquitous NaInternational journal of molecular sciences · 2022Review
- The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity.Frontiers in physiology · 2022Review
- NHE8 Deficiency Promotes Colitis-Associated Cancer in Mice via Expansion of Lgr5-Expressing Cells.Cellular and molecular gastroenterology and hepatology · 2019Article
- Tumor necrosis factor alpha reduces intestinal vitamin C uptake: a role for NF-κB-mediated signaling.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- SLC9 Gene Family: Function, Expression, and Regulation.Comprehensive Physiology · 2018Review
- Pathophysiology of IBD associated diarrhea.Tissue barriers · 2018Review
- Role of renal transporters and novel regulatory interactions in the TAL that control blood pressure.Physiological genomics · 2017Review
- Pathophysiology of Intestinal NaCellular and molecular gastroenterology and hepatology · 2017Article
- Somatostatin regulates NHE8 protein expression via the ERK1/2 MAPK pathway in DSS-induced colitis mice.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Intestinal NHE8 is highly expressed in goblet cells and its expression is subject to TNF-α regulation.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Protein-DNA Interactions at the Opossum Npt2a Promoter are Dependent upon NHERF-1.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2016Article
- Loss of NHE8 expression impairs intestinal mucosal integrity.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Sodium butyrate stimulates NHE8 expression via its role on activating NHE8 basal promoter activity.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Epithelial transport in inflammatory bowel diseases.Inflammatory bowel diseases · 2014Review
- NHE8 plays an important role in mucosal protection via its effect on bacterial adhesion.American journal of physiology. Cell physiology · 2013Article
- NHE8 plays important roles in gastric mucosal protection.American journal of physiology. Gastrointestinal and liver physiology · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
NHE8 transporter is a member of the sodium/hydrogen exchanger (NHE) family. This transporter protein is expressed at the apical membrane of epithelial cells of kidney and intestine and contributes to vectorial Na(+) transport in both tissues. Although NaCl absorption has been shown to be reduced in diarrhea associated with colitis and enteritis, little is known about the role of Na(+)/H(+) exchange and the involvement of NHE isoforms in the pathogenesis of inflammatory disorders and the mechanism of inflammation-associated diarrhea. This study investigated the role of NHE8 in the setting of inflammatory states. Jejunal mucosa was harvested from trinitrobenzene sulfonic acid (TNBS) colitis rats or lipopolysaccharide (LPS) rats for RNA extraction and brush-border membrane protein purification. The human NHE8 gene promoter was cloned from human genomic DNA and characterized in Caco-2 cells. The promoter was further used to study the mechanisms of TNF-alpha-mediated NHE8 expression downregulation in Caco-2 cells. Results from Western blot and real-time PCR indicated that NHE8 protein and mRNA were significantly reduced in TNBS rats and LPS rats. In Caco-2 cells, TNF-alpha produces similar reduction levels in the endogenous NHE8 mRNA expression observed in our in vivo studies. The downregulation of NHE8 expression mediated by TNF-alpha could be blocked by transcription inhibitor actinomycin D, suggesting the involvement of transcriptional regulation. Further studies indicated that the human NHE8 gene transcription could be activated by Sp3 transcriptional factor, and TNF-alpha inhibits human NHE8 expression by reducing Sp3 interaction at the minimal promoter region of the human NHE8 gene. In conclusion, our studies suggest that TNF-alpha decreases NHE8 expression in inflammation induced by TNBS and LPS, which may contribute to the diarrhea associated with inflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.