Uromodulin biology

Abstract

Uromodulin is a kidney-specific glycoprotein which is exclusively produced by the epithelial cells lining the thick ascending limb and early distal convoluted tubule. It is currently recognized as a multifaceted player in kidney physiology and disease, with discrete roles for intracellular, urinary, interstitial, and serum uromodulin. Among them, uromodulin modulates renal sodium handling through the regulation of tubular sodium transporters that reabsorb sodium and are targeted by diuretics, such as the loop diuretic-sensitive Na+-K+-2Cl− cotransporter type 2 (NKCC2) and the thiazide-sensitive Na+/Cl− cotransporter (NCC). Given these roles, the contribution of uromodulin to sodium-sensitive hypertension has been proposed. However, recent studies in humans suggest a more complex interaction between dietary sodium intake, uromodulin, and blood pressure. This review presents an updated overview of the uromodulin's biology and its various roles and focuses on the interaction between uromodulin and sodium-sensitive hypertension.

The role of uromodulin in cardiovascular disease: a review

“…The presence of sialic acid residues renders the protein highly acidic ( 17 ), with an isoelectric point of about 3.5 ( 18 ). Structurally, uromodulin encompasses multiple domains, including four epidermal growth factor (EGF)-like domains, a cysteine-rich domain (D8C) of unclear function, an internal hydrophobic plaque (IHP), and a dichotomous zona pellucida (ZP) domain facilitating protein polymerization ( 19 ) (As shown in Figure 1 ). The zona pellucida is followed by the external hydrophobic sheet (EHP) and the glycophosphatidylinositol(GPI) ancho.…”