ArticleProceedings of the National Academy of Sciences of the United States of America2019
Remote sensing and signaling in kidney proximal tubules stimulates gut microbiome-derived organic anion secretion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Uremic Toxins in Organ Crosstalk.Frontiers in medicine · 2021Pooled it
- A Randomized Trial of Distal Diuretics versus Dietary Sodium Restriction for Hypertension in Chronic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2020Trial
- A Kidney-Microbiome Short- and Medium-Chain Fatty Acid Loop Mediated by OAT1: Implications for the Remote Sensing and Signaling Theory.International journal of molecular sciences · 2026Article
- Transition to fetal calf serum-free culture enhances kidney proximal tubule cell bioenergetics and allows pharmacological applications.Cell and tissue research · 2026Article
- Article
- Aryl hydrocarbon receptor in the kidney regulates metabolic cross-talk with the liver and gut microbiome.Scientific reports · 2026Article
- A guide to uraemic toxicity.Nature reviews. Nephrology · 2026Review
- Microbes and GFR in Health and CKD in Mice.Journal of the American Society of Nephrology : JASN · 2026Article
- Developmentally dynamic chromatin state at loci regulating organ crosstalk by remote sensing and signaling.Epigenetics & chromatin · 2025Article
- Article
- Uremic toxins levels are associated with miR-223 in chronic kidney disease-associated anemia.Non-coding RNA research · 2025Article
- Estimation of Proximal Tubular Function by Stimulation of Organic Anion and Cation Transporters.Journal of the American Society of Nephrology : JASN · 2025Article
- Renal organic anion transporter 1: clinical relevance and the underlying mechanisms in chronic kidney disease.BMC nephrology · 2025Review
- Unveiling the role of sex in the metabolism of indoxyl sulfate and apixaban.Scientific reports · 2025Article
- Biology of the proximal tubule in body homeostasis and kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Gut-X axis.iMeta · 2025Review
- Proximal tubule-on-chip as a model for predicting cation transport and drug transporter dynamics.Scientific reports · 2025Article
- Recent Advances on the Regulations of Organic Anion Transporters.Pharmaceutics · 2024Review
- Uremic toxins mediate kidney diseases: the role of aryl hydrocarbon receptor.Cellular & molecular biology letters · 2024Review
- Remote effects of kidney drug transporter OAT1 on gut microbiome composition and urate homeostasis.JCI insight · 2023Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Membrane transporters and receptors are responsible for balancing nutrient and metabolite levels to aid body homeostasis. Here, we report that proximal tubule cells in kidneys sense elevated endogenous, gut microbiome-derived, metabolite levels through EGF receptors and downstream signaling to induce their secretion by up-regulating the organic anion transporter-1 (OAT1). Remote metabolite sensing and signaling was observed in kidneys from healthy volunteers and rats in vivo, leading to induced OAT1 expression and increased removal of indoxyl sulfate, a prototypical microbiome-derived metabolite and uremic toxin. Using 2D and 3D human proximal tubule cell models, we show that indoxyl sulfate induces OAT1 via AhR and EGFR signaling, controlled by miR-223. Concomitantly produced reactive oxygen species (ROS) control OAT1 activity and are balanced by the glutathione pathway, as confirmed by cellular metabolomic profiling. Collectively, we demonstrate remote metabolite sensing and signaling as an effective OAT1 regulation mechanism to maintain plasma metabolite levels by controlling their secretion.
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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.