ArticleScientific reports2019
The Urinary Excretion of Uromodulin is Regulated by the Potassium Channel ROMK.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Is uromodulin a reliable biomarker in pediatric vesicoureteral reflux? An exploratory pilot study.International urology and nephrology · 2026Article
- 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
- Characterizing molecular and behavioral changes arising from ROMK potassium channel deficiency in the cerebellum.Frontiers in behavioral neuroscience · 2025Article
- Advances in uromodulin biology and potential clinical applications.Nature reviews. Nephrology · 2024Review
- Insights into Uromodulin and Blood Pressure.Current hypertension reports · 2024Review
- Integrative single-cell characterization of a frugivorous and an insectivorous bat kidney and pancreas.Nature communications · 2024Article
- The role of uromodulin in cardiovascular disease: a review.Frontiers in cardiovascular medicine · 2024Review
- Allelic effects on uromodulin aggregates drive autosomal dominant tubulointerstitial kidney disease.EMBO molecular medicine · 2023Article
- Role of Uromodulin in Salt-Sensitive Hypertension.Hypertension (Dallas, Tex. : 1979) · 2022Review
- UMOD and the architecture of kidney disease.Pflugers Archiv : European journal of physiology · 2022Review
- Role of uromodulin and complement activation in the progression of kidney disease.Oncology letters · 2021Article
- Molecular Basis, Diagnostic Challenges and Therapeutic Approaches of Bartter and Gitelman Syndromes: A Primer for Clinicians.International journal of molecular sciences · 2021Review
- SeqStain is an efficient method for multiplexed, spatialomic profiling of human and murine tissues.Cell reports methods · 2021Article
- NaCl cotransporter activity and MgAmerican journal of physiology. Renal physiology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Uromodulin, the most abundant protein in normal urine, is produced by cells lining the thick ascending limb (TAL) of the loop of Henle. Uromodulin regulates the activity of the potassium channel ROMK in TAL cells. Common variants in KCNJ1, the gene encoding ROMK, are associated with urinary levels of uromodulin in population studies. Here, we investigated the functional link between ROMK and uromodulin in Kcnj1 knock-out mouse models, in primary cultures of mouse TAL (mTAL) cells, and in patients with Bartter syndrome due to KCNJ1 mutations. Both global and kidney-specific Kcnj1 knock-out mice showed reduced urinary levels of uromodulin paralleled by increased levels in the kidney, compared to wild-type controls. Pharmacological inhibition and genetic deletion of ROMK in mTAL cells caused a reduction in apical uromodulin excretion, reflected by cellular accumulation. In contrast, NKCC2 inhibition showed no effect on uromodulin processing. Patients with Bartter syndrome type 2 showed reduced urinary uromodulin levels compared to age and gender matched controls. These results demonstrate that ROMK directly regulates processing and release of uromodulin by TAL cells, independently from NKCC2. They support the functional link between transport activity and uromodulin in the TAL, relevant for blood pressure control and urinary concentrating ability.
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