Evolving Concepts in Uromodulin Biology, Physiology, and Its Role in Disease: a Tale of Two Forms

If you need an accessible version of this item, please submit a remediation request.
Date
2022-11
Language
American English
Embargo Lift Date
Committee Members
Degree
Degree Year
Department
Grantor
Journal Title
Journal ISSN
Volume Title
Found At
American Heart Association
Abstract

Uromodulin (or Tamm-Horsfall protein) is a glycoprotein uniquely produced in the kidney by tubular cells of the thick ascending limb of the loop of Henle and early distal tubules. This protein exhibits bidirectional secretion in the urine and in the renal interstitium and circulation. The role of this protein in maintaining renal and systemic homeostasis is becoming increasingly appreciated. Furthermore, perturbations of its functions may play a role in various diseases affecting the kidney and distant organs. In this review, we will discuss important advances in understanding its biology, highlighting the recent discoveries of its secretion and differential precursor processing that generates two forms: a) a highly polymerizing form that is apically excreted in the urine and generates filaments, and b) a non-polymerizing form that retains a polymerization inhibitory pro-peptide and is released basolaterally in the kidney interstitium and circulation, but can also be found in the urine. We will also discuss factors regulating its production and release, taking into account its intricate physiology, and propose best practices to report its levels. We also discuss breaking advances in its role in hypertension, acute kidney injury and progression to chronic disease, immunomodulation and regulating renal and systemic oxidative stress. We anticipate that this work will be a great resource for researchers and clinicians. This review will highlight the importance of defining what regulates the two forms of uromodulin, so that modulation of uromodulin levels and function could become a novel tool in our therapeutic armamentarium against kidney disease.

Description
item.page.description.tableofcontents
item.page.relation.haspart
Cite As
LaFavers, K. A., Micanovic, R., Sabo, A. R., Maghak, L. A., & El-Achkar, T. M. (2022). Evolving Concepts in Uromodulin Biology, Physiology, and Its Role in Disease: A Tale of Two Forms. Hypertension, 79(11), 2409–2418. https://doi.org/10.1161/HYPERTENSIONAHA.122.18567
ISSN
Publisher
Series/Report
Sponsorship
Major
Extent
Identifier
Relation
Journal
Hypertension
Source
PMC
Alternative Title
Type
Article
Number
Volume
Conference Dates
Conference Host
Conference Location
Conference Name
Conference Panel
Conference Secretariat Location
Version
Author's manuscript
Full Text Available at
This item is under embargo {{howLong}}