ArticleScientific reports2019
Hepsin-mediated Processing of Uromodulin is Crucial for Salt-sensitivity and Thick Ascending Limb Homeostasis.
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 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Urinary extracellular vesicles: A position paper by the Urine Task Force of the International Society for Extracellular Vesicles.Journal of extracellular vesicles · 2021Guideline
- The Relationship Between Urine Uromodulin and Blood Pressure Changes: The DASH-Sodium Trial.American journal of hypertension · 2021Trial
- Endocrine regulation of uromodulin in aging.Frontiers in endocrinology · 2026Review
- Early renal response to long-term salt loading: mitochondrial dysfunction, ER stress, and uromodulin accumulation in the kidney medulla.American journal of physiology. Renal physiology · 2025Article
- A salty symphony: unraveling the tale of uromodulin and sodium sensitivity.Journal of human hypertension · 2025Review
- Disrupted uromodulin trafficking is rescued by targeting TMED cargo receptors.The Journal of clinical investigation · 2024Article
- Advances in uromodulin biology and potential clinical applications.Nature reviews. Nephrology · 2024Review
- Zinc deficiency induces hypertension by paradoxically amplifying salt sensitivity under high salt intake in mice.Clinical and experimental nephrology · 2024Article
- Uromodulin biology.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- The Versatile Role of Uromodulin in Renal Homeostasis and Its Relevance in Chronic Kidney Disease.Internal medicine (Tokyo, Japan) · 2024Review
- Allelic effects on uromodulin aggregates drive autosomal dominant tubulointerstitial kidney disease.EMBO molecular medicine · 2023Article
- Type II Transmembrane Serine Proteases as Modulators in Adipose Tissue Phenotype and Function.Biomedicines · 2023Review
- Evolving Concepts in Uromodulin Biology, Physiology, and Its Role in Disease: a Tale of Two Forms.Hypertension (Dallas, Tex. : 1979) · 2022Review
- Role of Uromodulin in Salt-Sensitive Hypertension.Hypertension (Dallas, Tex. : 1979) · 2022Review
- The Post-Translational Modification Networking in WNK-Centric Hypertension Regulation and Electrolyte Homeostasis.Biomedicines · 2022Review
- Uromodulin Regulates Murine Aquaporin-2 Activity via Thick Ascending Limb-Collecting Duct Cross-Talk during Water Deprivation.International journal of molecular sciences · 2022Article
- UMOD and the architecture of kidney disease.Pflugers Archiv : European journal of physiology · 2022Review
- The kidney protects against sepsis by producing systemic uromodulin.American journal of physiology. Renal physiology · 2022Article
- The kidney releases a nonpolymerizing form of uromodulin in the urine and circulation that retains the external hydrophobic patch domain.American journal of physiology. Renal physiology · 2022Article
- Salt loading decreases urinary excretion and increases intracellular accumulation of uromodulin in stroke-prone spontaneously hypertensive rats.Clinical science (London, England : 1979) · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Uromodulin is a zona pellucida-type protein essentially produced in the thick ascending limb (TAL) of the mammalian kidney. It is the most abundant protein in normal urine. Defective uromodulin processing is associated with various kidney disorders. The luminal release and subsequent polymerization of uromodulin depend on its cleavage mediated by the serine protease hepsin. The biological relevance of a proper cleavage of uromodulin remains unknown. Here we combined in vivo testing on hepsin-deficient mice, ex vivo analyses on isolated tubules and in vitro studies on TAL cells to demonstrate that hepsin influence on uromodulin processing is an important modulator of salt transport via the sodium cotransporter NKCC2 in the TAL. At baseline, hepsin-deficient mice accumulate uromodulin, along with hyperactivated NKCC2, resulting in a positive sodium balance and a better adaptation to water deprivation. In conditions of high salt intake, defective uromodulin processing predisposes hepsin-deficient mice to a salt-wasting phenotype, with a decreased salt sensitivity. These modifications are associated with intracellular accumulation of uromodulin, endoplasmic reticulum-stress and signs of tubular damage. These studies expand the physiological role of hepsin and uromodulin and highlight the importance of hepsin-mediated processing of uromodulin for kidney tubule homeostasis and salt sensitivity.
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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 Socratic graph.