Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 552763
Title Remote sensing and signaling in kidney proximal tubules stimulates gut microbiome-derived organic anion secretion
Author(s) Jansen, Jitske; Jansen, Katja; Neven, Ellen; Poesen, Ruben; Othman, Amr; Mil, Alain van; Sluijter, Joost; Torano, Javier Sastre; Zaal, Esther A.; Berkers, Celia R.; Esser, Diederik; Wichers, Harry J.; Ede, Karin van; Duursen, Majorie van; Burtey, Stéphane; Verhaar, Marianne C.; Meijers, Björn; Masereeuw, Rosalinde
Source Proceedings of the National Academy of Sciences of the United States of America 116 (2019)32. - ISSN 0027-8424 - p. 16105 - 16110.
DOI https://doi.org/10.1073/pnas.1821809116
Department(s) Food, Health & Consumer Research
VLAG
Toxicology Postdoc
Publication type Refereed Article in a scientific journal
Publication year 2019
Keyword(s) Indoxyl sulfate - Kidney proximal tubule - Organic anion transporter 1 - Remote sensing and signaling
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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