ArticleKidney international2013
Uromodulin upregulates TRPV5 by impairing caveolin-mediated endocytosis.
Article in Kidney international, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 77 citations in OpenAlex.
- Exploring promising biomarkers based on pathogenic mechanisms in interstitial cystitis/bladder pain syndrome.Nature reviews. Urology · 2026Review
- Recent advances in the clinical significance and physiological functions of uromodulin: a narrative review.BMC nephrology · 2026Review
- Endocrine regulation of uromodulin in aging.Frontiers in endocrinology · 2026Review
- A Multiomics Study of Circulating Proteins and Kidney Stone Risk.Journal of the American Society of Nephrology : JASN · 2025Article
- Autosomal dominant tubulointerstitial kidney disease-UMOD: a short review.Orphanet journal of rare diseases · 2025Review
- A salty symphony: unraveling the tale of uromodulin and sodium sensitivity.Journal of human hypertension · 2025Review
- Advances in uromodulin biology and potential clinical applications.Nature reviews. Nephrology · 2024Review
- Calmodulin regulates TRPV5 intracellular trafficking and plasma membrane abundance.The Journal of physiology · 2024Article
- Serum uromodulin associates with kidney function and outcome in a cohort of hospitalised COVID-19 patients.Scientific reports · 2024Article
- Review
- Exosomal UMOD gene expression and urinary uromodulin level as early noninvasive diagnostic biomarkers for diabetic nephropathy in type 2 diabetic patients.Diabetology international · 2024Article
- Uromodulin biology.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- A DNA nanostructure-Hif-1α inducer complex as novel nanotherapy against cisplatin-induced acute kidney injury.Cell proliferation · 2024Article
- The Versatile Role of Uromodulin in Renal Homeostasis and Its Relevance in Chronic Kidney Disease.Internal medicine (Tokyo, Japan) · 2024Review
- The role of uromodulin in cardiovascular disease: a review.Frontiers in cardiovascular medicine · 2024Review
- Unveiling the Hidden Power of Uromodulin: A Promising Potential Biomarker for Kidney Diseases.Diagnostics (Basel, Switzerland) · 2023Review
- 24-h Urinary Calcium Excretion and Renal Outcomes in Hospitalized Patients with and without Chronic Kidney Disease.Journal of clinical medicine · 2023Article
- Kidney function may partially mediated the protective effect of urinary uromodulin on kidney stone.Urolithiasis · 2023Article
- Influence of glycoprotein MUC1 on trafficking of the CaThe Journal of biological chemistry · 2023Article
- Role of Uromodulin in Salt-Sensitive Hypertension.Hypertension (Dallas, Tex. : 1979) · 2022Review
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3 authors at 3 institutions in 1 country.
Funding
Abstract
Uromodulin (UMOD) is synthesized in the thick ascending limb and secreted into urine as the most abundant protein. Association studies in humans suggest protective effects of UMOD against calcium-containing kidney stones. Mice carrying mutations of Umod found in human UMOD-associated kidney disease (UAKD) and Umod-deficient mice exhibit hypercalciuria. The mechanism for UMOD regulation of urinary Ca(2+) excretion is incompletely understood. We examined if UMOD regulates TRPV5 and TRPV6, channels critical for renal transcellular Ca(2+) reabsorption. Coexpression with UMOD increased whole-cell TRPV5 current density in HEK293 cells. In biotinylation studies, UMOD increased TRPV5 cell-surface abundance. Extracellular application of purified UMOD upregulated TRPV5 current density within physiological relevant concentration ranges. UMOD exerted a similar effect on TRPV6. TRPV5 undergoes constitutive caveolin-mediated endocytosis. UMOD had no effect on TRPV5 in a caveolin-1-deficient cell line. Expression of recombinant caveolin-1 in these cells restored the ability of UMOD to upregulate TRPV5. Secretion of UAKD-mutant UMOD was markedly reduced and coexpression of mutant UMOD with TRPV5 failed to increase its current. Immunofluorescent studies demonstrated lower TRPV5 expression in Umod(-/-) mice compared with wild-type. UMOD upregulates TRPV5 by acting from extracellular and by decreasing endocytosis of TRPV5. The stimulation of Ca(2+) reabsorption via TRPV5 by UMOD may contribute to protection against kidney-stone formation.
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