ArticlePflugers Archiv : European journal of physiology2015
Evidence for a causal link between adaptor protein PDZK1 downregulation and Na⁺/H⁺ exchanger NHE3 dysfunction in human and murine colitis.
Article in Pflugers Archiv : European journal of physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Plasma Proteomic Signatures of Glucose Metabolism Disturbances and Early Diabetes.International journal of molecular sciences · 2026Article
- Shared genetic architecture between schizophrenia and gastrointestinal diseases: insights from large-scale genome-wide cross-trait analysis.Annals of general psychiatry · 2026Article
- New functions of enzymatic cottonseed protein: Improvement of intestinal digestion and absorption, structure and microbial composition of juvenile yellow catfish (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- IQGAP-2: a novel interacting partner with the human colonic thiamin pyrophosphate transporter.American journal of physiology. Cell physiology · 2024Article
- The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity.Frontiers in physiology · 2022Review
- Ion Transport Basis of Diarrhea in a Mouse Model of Adoptive T Cell Transfer Colitis.Digestive diseases and sciences · 2020Article
- Impairment of electroneutral NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Calcium-sensing receptor regulates intestinal dipeptide absorption via CaPhysiological reports · 2020Article
- Identification of transmembrane protein 237 as a novel interactor with the intestinal riboflavin transporter-3 (RFVT-3): role in functionality and cell biology.American journal of physiology. Cell physiology · 2019Article
- Expression, Localization and Functional Activity of the Major Na⁺/H⁺ Exchange Isoforms Expressed in the Intestinal Cell Line Caco-2BBe.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2019Article
- Inhibition of autotaxin alleviates inflammation and increases the expression of sodium-dependent glucose cotransporter 1 and NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Microbial dysbiosis associated with impaired intestinal NaMucosal immunology · 2018Article
- Restoration of mucosal integrity and epithelial transport function by concomitant anti-TNFα treatment in chronic DSS-induced colitis.Journal of molecular medicine (Berlin, Germany) · 2018Article
- NHERF1 Between Promises and Hopes: Overview on Cancer and Prospective Openings.Translational oncology · 2018Review
- Tumor necrosis factor-α acts reciprocally with solute carrier family 26, member 3, (downregulated-in-adenoma) and reduces its expression, leading to intestinal inflammation.International journal of molecular medicine · 2018Article
- Soluble uric acid increases PDZK1 and ABCG2 expression in human intestinal cell lines via the TLR4-NLRP3 inflammasome and PI3K/Akt signaling pathway.Arthritis research & therapy · 2018Article
- Pathophysiology of IBD associated diarrhea.Tissue barriers · 2018Review
- IL-1β-Induced Downregulation of the Multifunctional PDZ Adaptor PDZK1 Is Attenuated by ERK Inhibition, RXRα, or PPARα Stimulation in Enterocytes.Frontiers in physiology · 2017Article
- Mechanisms Underlying Dysregulation of Electrolyte Absorption in Inflammatory Bowel Disease-Associated Diarrhea.Inflammatory bowel diseases · 2015Review
- Assessment of a molecular diagnostic platform for integrated isolation and quantification of mRNA in whole blood.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2015Article
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
A dysfunction of the Na(+)/H(+) exchanger isoform 3 (NHE3) significantly contributes to the reduced salt absorptive capacity of the inflamed intestine. We previously reported a strong decrease in the NHERF family member PDZK1 (NHERF3), which binds to NHE3 and regulates its function in a mouse model of colitis. The present study investigates whether a causal relationship exists between the decreased PDZK1 expression and the NHE3 dysfunction in human and murine intestinal inflammation. Biopsies from the colon of patients with ulcerative colitis, murine inflamed ileal and colonic mucosa, NHE3-transfected Caco-2BBe colonic cells with short hairpin RNA (shRNA) knockdown of PDZK1, and Pdzk1-gene-deleted mice were studied. PDZK1 mRNA and protein expression was strongly decreased in inflamed human and murine intestinal tissue as compared to inactive disease or control tissue, whereas that of NHE3 or NHERF1 was not. Inflamed human and murine intestinal tissues displayed correct brush border localization of NHE3 but reduced acid-activated NHE3 transport activity. A similar NHE3 transport defect was observed when PDZK1 protein content was decreased by shRNA knockdown in Caco-2BBe cells or when enterocyte PDZK1 protein content was decreased to similar levels as found in inflamed mucosa by heterozygote breeding of Pdzk1-gene-deleted and WT mice. We conclude that a decrease in PDZK1 expression, whether induced by inflammation, shRNA-mediated knockdown, or heterozygous breeding, is associated with a decreased NHE3 transport rate in human and murine enterocytes. We therefore hypothesize that inflammation-induced loss of PDZK1 expression may contribute to the NHE3 dysfunction observed in the inflamed intestine.
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