Schaeffer Céline, Devuyst Olivier, Rampoldi Luca
Molecular Genetics of Renal Disorders, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy; email:
Mechanisms of Inherited Kidney Disorders Group, University of Zurich, CH-8057 Zurich, Switzerland.
Annu Rev Physiol. 2021 Feb 10;83:477-501. doi: 10.1146/annurev-physiol-031620-092817.
Uromodulin, a protein exclusively produced by the kidney, is the most abundant urinary protein in physiological conditions. Already described several decades ago, uromodulin has gained the spotlight in recent years, since the discovery that mutations in its encoding gene cause a renal Mendelian disease (autosomal dominant tubulointerstitial kidney disease) and that common polymorphisms are associated with multifactorial disorders, such as chronic kidney disease, hypertension, and cardiovascular diseases. Moreover, variations in uromodulin levels in urine and/or blood reflect kidney functioning mass and are of prognostic value for renal function, cardiovascular events, and overall mortality. The clinical relevance of uromodulin reflects its multifunctional nature, playing a role in renal ion transport and immunomodulation, in protection against urinary tract infections and renal stones, and possibly as a systemic antioxidant. Here, we discuss the multifaceted roles of this protein in kidney physiology and its translational relevance.
尿调节蛋白是一种仅由肾脏产生的蛋白质，在生理条件下是尿液中含量最丰富的蛋白质。几十年前就已有相关描述，近年来尿调节蛋白备受关注，因为发现其编码基因突变会导致一种肾脏孟德尔疾病（常染色体显性肾小管间质性肾病），且常见的基因多态性与慢性肾病、高血压和心血管疾病等多因素疾病有关。此外，尿液和/或血液中尿调节蛋白水平的变化反映了肾脏的功能质量，对肾功能、心血管事件和总体死亡率具有预后价值。尿调节蛋白的临床相关性反映了其多功能特性，它在肾脏离子转运和免疫调节中发挥作用，可预防尿路感染和肾结石，还可能作为一种全身抗氧化剂。在此，我们讨论这种蛋白质在肾脏生理学中的多方面作用及其转化相关性。
