Article ; Online: Evolving Concepts in Uromodulin Biology, Physiology, and Its Role in Disease: a Tale of Two Forms.
Hypertension (Dallas, Tex. : 1979)
2022 Volume 79, Issue 11, Page(s) 2409–2418
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 ... ...
| 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 2 forms: (1) a highly polymerizing form that is apically excreted in the urine and generates filaments and (2) a nonpolymerizing 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 2 forms of uromodulin, so that modulation of uromodulin levels and function could become a novel tool in our therapeutic armamentarium against kidney disease. |
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| MeSH term(s) | Humans ; Uromodulin/metabolism ; Kidney/metabolism ; Acute Kidney Injury/metabolism ; Hypertension/metabolism ; Biology | |||||
| Chemical Substances | Uromodulin | |||||
| Language | English | |||||
| Publishing date | 2022-08-12 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. | |||||
| ZDB-ID | 423736-5 | |||||
| ISSN | 1524-4563 ; 0194-911X ; 0362-4323 | |||||
| ISSN (online) | 1524-4563 | |||||
| ISSN | 0194-911X ; 0362-4323 | |||||
| DOI | 10.1161/HYPERTENSIONAHA.122.18567 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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