{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:02:01Z","timestamp":1784869321652,"version":"3.55.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>\n                    Claudin-3 is a tight junction protein expressed in the distal nephron, notably in the thick ascending limb of Henle\u2019s loop and the distal convoluted tubule, where it acts as an aldosterone-regulated paracellular barrier to sodium and chloride transport. Here, we demonstrate that claudin-3 knockout (KO) mice exhibit an unexpected diet-dependent alteration in glomerular filtration rate (GFR): under a normal sodium (NS) diet, GFR decreases significantly, whereas under a low sodium (LS) diet, GFR increases paradoxically compared with wild-type controls. To identify the underlying mechanism, we examined claudin-3 expression in the\n                    <jats:italic>macula densa<\/jats:italic>\n                    , the specialized epithelial structure located at the junction between the thick ascending limb and the distal convoluted tubule that governs tubuloglomerular feedback (TGF). Immunofluorescence analysis revealed that claudin-3 colocalizes with neuronal nitric oxide synthase (nNOS) and the Na\n                    <jats:sup>+<\/jats:sup>\n                    -K\n                    <jats:sup>+<\/jats:sup>\n                    -2Cl\n                    <jats:sup>-<\/jats:sup>\n                    cotransporter (NKCC2) in a distinct cluster of cells characterized by densely packed nuclei, positioned in direct contact with the glomerulus and immediately adjacent to an NCC-positive distal convoluted tubule, while remaining itself NCC-negative. Notably, within the tubule containing the\n                    <jats:italic>macula densa<\/jats:italic>\n                    , nNOS expression was strictly confined to\n                    <jats:italic>macula densa<\/jats:italic>\n                    cells, clearly distinguishing them from the surrounding tubular epithelium. These results identify claudin-3 as a previously unrecognized component of\n                    <jats:italic>macula densa<\/jats:italic>\n                    biology and suggest a role for claudin-3 in the control of GFR possibly\n                    <jats:italic>via<\/jats:italic>\n                    the tubuloglomerular feedback.\n                  <\/jats:p>","DOI":"10.3389\/fphys.2026.1869073","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:22:57Z","timestamp":1784866977000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Claudin-3 is expressed at the macula densa and is associated with altered glomerular filtration in claudin-3 knockout mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Alexandra","family":"Chassot","sequence":"first","affiliation":[{"name":"Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Feraille","sequence":"additional","affiliation":[{"name":"Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Sassi","sequence":"additional","affiliation":[{"name":"Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.kint.2021.02.023","article-title":"A novel claudin-10 mutation with a unique mechanism in two unrelated families with HELIX syndrome","volume":"100","author":"Alzahrani","year":"2021","journal-title":"Kidney Int."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1101\/2025.01.09.631985","article-title":"Tissular glucocorticoid reactivating enzyme 11beta-HSD1 drives pathogenic myofibroblast differentiation in chronic kidney disease","author":"Arnoux","year":"2025"},{"key":"B3","doi-asserted-by":"publisher","first-page":"F885","DOI":"10.1152\/ajprenal.1995.268.5.F885","article-title":"Topography of nitric oxide synthesis by localizing constitutive NO synthases in mammalian kidney","volume":"268","author":"Bachmann","year":"1995","journal-title":"Am. 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