ArticleArthritis research & therapy2018
Soluble uric acid increases PDZK1 and ABCG2 expression in human intestinal cell lines via the TLR4-NLRP3 inflammasome and PI3K/Akt signaling pathway.
Article in Arthritis research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.
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Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 116 citations in OpenAlex.
- Role and mechanisms of SGLT-2 inhibitors in the treatment of diabetic kidney disease.Frontiers in immunology · 2023Pooled it
- Uremic Toxins in Organ Crosstalk.Frontiers in medicine · 2021Pooled it
- Serum uric acid and its metabolism-a vital factor in the inflammatory transformation of cancer.Journal of advanced research · 2026Review
- Gut microbiota Lactobacillus johnsonii alleviates hyperuricemia by modulating intestinal urate and gut microbiota-derived butyrate.Chinese medical journal · 2026Article
- Effect of Probiotic Product Containing Heyndrickxia coagulans TBC169 on Hyperuricemia in Rats.Probiotics and antimicrobial proteins · 2026Article
- The interplay between NLRP3 inflammasome and metabolic signals in gouty arthritis.Frontiers in immunology · 2026Review
- Effects of hydroxypropyl starch on intestinal health and transcriptome of geese.Scientific reports · 2025Article
- From Endoscopic Inspection to Gene-Expression: A Thorough Assessment of the Duodenal Mucosa After Resurfacing-A Prospective Study.Digestive diseases and sciences · 2025Article
- Overview of pharmacodynamical research of traditional Chinese medicine on hyperuricemic nephropathy: from the perspective of dual-regulatory effect on the intestines and kidneys.Frontiers in pharmacology · 2025Review
- Genome-wide association studies and traditional Chinese medicine in hyperuricemia: current evidence and mechanistic insights.Frontiers in pharmacology · 2025Review
- Association betweenFrontiers in medicine · 2025Article
- Hyperuricemia and its related diseases: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2024Review
- The pathogenesis of gout: molecular insights from genetic, epigenomic and transcriptomic studies.Nature reviews. Rheumatology · 2024Review
- miR-101-3p-mediated role of PDZK1 in hepatocellular carcinoma progression and the underlying PI3K/Akt signaling mechanism.Cell division · 2024Article
- Article
- Emerging Urate-Lowering Drugs and Pharmacologic Treatment Strategies for Gout: A Narrative Review.Drugs · 2023Review
- Inhibition of the uric acid efflux transporter ABCG2 enhances stimulating effect of soluble uric acid on IL-1β production in murine macrophage-like J774.1 cells.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Article
- Biodegradation of Uric Acid byMicroorganisms · 2023Article
- Anti-Hyperuricemic Effect of Anserine Based on the Gut-Kidney Axis: Integrated Analysis of Metagenomics and Metabolomics.Nutrients · 2023Article
- Role of Uric Acid in Vascular Remodeling: Cytoskeleton Changes and Migration in VSMCs.International journal of molecular sciences · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn addition to the kidney, the intestine is one of the most important organs involved in uric acid excretion. However, the mechanism of urate excretion in the intestine remains unclear. Therefore, the relationship between soluble uric acid and the gut excretion in human intestinal cells was explored. The relevant signaling molecules were then also examined.
methodsHT-29 and Caco-2 cell lines were stimulated with soluble uric acid. Western blotting and qRT-PCR were used to measure protein and mRNA levels. Subcellular fractionation methods and immunofluorescence were used to quantify the proteins in different subcellular compartments. Flow cytometry experiments examined the function of ATP-binding cassette transporter, subfamily G, member 2 (ABCG2). Small interfering RNA transfection was used to assess the interaction between ABCG2 and PDZ domain-containing 1 (PDZK1).
resultsSoluble uric acid increased the expression of PDZK1 and ABCG2. The stimulation of soluble uric acid also facilitated the translocation of ABCG2 from the intracellular compartment to the plasma membrane and increased its transport activity. Moreover, the upregulation of PDZK1 and ABCG2 by soluble uric acid was partially decreased by either TLR4-NLRP3 inflammasome inhibitors or PI3K/Akt signaling inhibitors. Furthermore, PDZK1 knockdown significantly inhibited the expression and transport activity of ABCG2 regardless of the activation by soluble uric acid, demonstrating a pivotal role for PDZK1 in the regulation of ABCG2.
conclusionsThese findings suggest that urate upregulates the expression of PDZK1 and ABCG2 for excretion in intestinal cells via activating the TLR4-NLRP3 inflammasome and PI3K/Akt signaling pathway.
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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.