ArticleThe Biochemical journal2006
Transcriptional stimulation of the human NHE3 promoter activity by PMA: PKC independence and involvement of the transcription factor EGR-1.
Article in The Biochemical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity.Frontiers in physiology · 2022Review
- Gut-associated cGMP mediates colitis and dysbiosis in a mouse model of an activating mutation in GUCY2C.The Journal of experimental medicine · 2021Article
- Solute carrier family 9, subfamily A, member 3 (SLC9A3)/sodium-hydrogen exchanger member 3 (NHE3) dysregulation and dilated intercellular spaces in patients with eosinophilic esophagitis.The Journal of allergy and clinical immunology · 2018Article
- Epigenetic modulation of intestinal NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Human Clostridium difficile infection: inhibition of NHE3 and microbiota profile.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- PMA synergistically enhances apicularen A-induced cytotoxicity by disrupting microtubule networks in HeLa cells.BMC cancer · 2014Article
- Lactobacillus acidophilus upregulates intestinal NHE3 expression and function.American journal of physiology. Gastrointestinal and liver physiology · 2012Article
- PKCδ-dependent activation of ERK1/2 leads to upregulation of the human NHE2 transcriptional activity in intestinal epithelial cell line C2BBe1.American journal of physiology. Gastrointestinal and liver physiology · 2012Article
- The role of oct-1 in the regulation of tracheal antimicrobial peptide (TAP) and lingual antimicrobial peptide (LAP) expression in bovine mammary epithelial cells.Immunogenetics · 2011Article
- Transcriptional regulation of the intestinal luminal Na⁺ and Cl⁻ transporters.The Biochemical journal · 2011Review
- Tumor necrosis factor-α represses the expression of NHE2 through NF-κB activation in intestinal epithelial cell model, C2BBe1.Inflammatory bowel diseases · 2011Article
- Biosynthesis of promatrix metalloproteinase-9/chondroitin sulphate proteoglycan heteromer involves a Rottlerin-sensitive pathway.PloS one · 2011Article
- Transcriptional regulation of the human Na+/H+ exchanger NHE3 by serotonin in intestinal epithelial cells.Biochemical and biophysical research communications · 2009Article
- Luminal Na(+)/H (+) exchange in the proximal tubule.Pflugers Archiv : European journal of physiology · 2009Review
- PKC-dependent stimulation of the human MCT1 promoter involves transcription factor AP2.American journal of physiology. Gastrointestinal and liver physiology · 2009Article
- Characterization of the 5'-flanking region and regulation of expression of human anion exchanger SLC26A6.Journal of cellular biochemistry · 2008Article
- Sp1 and Sp3 control constitutive expression of the human NHE2 promoter by interactions with the proximal promoter and the transcription initiation site.The Biochemical journal · 2007Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
NHE3 (Na+/H+ exchanger 3) is essential for Na+ absorption in the ileum and is expressed in a cell-specific manner in the apical membrane of the intestinal epithelial cells. In the present study, we report the stimulatory effect of PMA on the hNHE3 (human NHE3) transcription. Pretreatment with actinomycin D or cycloheximide blocked the up-regulation of the NHE3 mRNA by PMA, indicating that the increased level of NHE3 mRNA expression is regulated by transcriptional activation and is dependent on de novo protein synthesis. 5'-Deletion of the promoter region and transfection analysis in C2BBe1 cells revealed that the PMA effect is mediated through a GC-rich DNA region between nt -88 and -69. Gel mobility-shift assays demonstrated that in nuclear extracts from C2BBe1 cells grown under the basal growth conditions, Sp1 (stimulating protein-1) and Sp3 interact with this GC-rich DNA region, while, in PMA-treated nuclear extracts, PMA-induced EGR-1 (early growth response gene product 1) transcription factor binds to the same site. Binding of EGR-1 diminished the Sp1 and Sp3 interactions with this promoter region significantly. Co-transfection of Sp1 or Sp3 into SL2 cells activated the NHE3-reporter constructs, suggesting that Sp1 and Sp3 act as positive regulators of the NHE3 expression. In addition, overexpression of EGR-1 was sufficient to transactivate the NHE3-reporter gene activity, and knockdown of EGR-1 with gene-specific small interfering RNA resulted in inhibition of the PMA-induced up-regulation of the endogenous NHE3 mRNA expression. Furthermore, the PKC (protein kinase C) inhibitor chelerythrine chloride did not affect PMA-induced NHE3 promoter activity, suggesting that PMA stimulation of the hNHE3 gene expression may be PKC-independent.
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