The rediscovery of uromodulin (Tamm-Horsfall protein): from tubulointerstitial nephropathy to chronic kidney disease
| Autor: | Antonio Amoroso, Olivier Devuyst, Francesco Scolari, Gian Marco Ghiggeri, Luca Rampoldi |
|---|---|
| Přispěvatelé: | University of Zurich, Rampoldi, L, Scolari, F, Amoroso, A, Ghiggeri, G, Devuyst, O |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Tamm–Horsfall protein uromodulin Urinary system 030232 urology & nephrology 610 Medicine & health Kidney 10052 Institute of Physiology 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Humans Genetic Predisposition to Disease genetics Hyperuricemia 030304 developmental biology 0303 health sciences 2727 Nephrology biology medullary cystic disease business.industry Kidney metabolism medicine.disease 3. Good health medicine.anatomical_structure Endocrinology Phenotype Nephrology 10076 Center for Integrative Human Physiology Knockout mouse Chronic Disease Mutation biology.protein Disease Progression Nephritis Interstitial 570 Life sciences Kidney Diseases business Nephritis Biomarkers chronic kidney disease Kidney disease Genome-Wide Association Study |
| Zdroj: | Kidney International; Vol 80 Kidney International |
| ISSN: | 1523-1755 |
| DOI: | 10.1038/ki.2011.134 |
| Popis: | Uromodulin (Tamm–Horsfall protein) is the most abundant protein excreted in the urine under physiological conditions. It is exclusively produced in the kidney and secreted into the urine via proteolytic cleavage. Its biological function is still not fully understood. Uromodulin has been linked to water/electrolyte balance and to kidney innate immunity. Also, studies in knockout mice demonstrated that it has a protective role against urinary tract infections and renal stone formation. Mutations in the gene encoding uromodulin lead to rare autosomal dominant diseases, collectively referred to as uromodulin-associated kidney diseases. They are characterized by progressive tubulointerstitial damage, impaired urinary concentrating ability, hyperuricemia, renal cysts, and progressive renal failure. Novel in vivo studies point at intracellular accumulation of mutant uromodulin as a key primary event in the disease pathogenesis. Recently, genome-wide association studies identified uromodulin as a risk factor for chronic kidney disease (CKD) and hypertension, and suggested that the level of uromodulin in the urine could represent a useful biomarker for the development of CKD. In this review, we summarize these recent investigations, ranging from invalidation studies in mouse to Mendelian disorders and genome-wide associations, which led to a rediscovery of uromodulin and boosted the scientific and clinical interest for this long discovered molecule. |
| Databáze: | OpenAIRE |
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