Both Tamm-Horsfall protein (THP) and collectin-11 (CL-11) are important molecules in acute kidney injury (AKI). In this study, we measured the change of glycosylation of THP in patients with AKI after surgery, using MALDI-TOF MS and lectin array analysis. The amount of high-mannose and core fucosylation in patients with AKI were higher than those in healthy controls. In vitro study showed that THP could bind to CL-11 with affinity at 9.41 × 10 −7 mol/L and inhibited activation of complement lectin pathway. The binding affinity decreased after removal of glycans on THP. Removal of fucose completely ablated the binding between the two proteins. While removal of high-mannose or part of the N-glycan decreased the binding ability to 30% or 60%.The results indicated that increase of fucose on THP played an important role via complement lectin pathway in AKI.
Uromodulin (UMOD, also called Tamm-Horsfall protein) has been gradually recognized as a protective factor and a biomarker of kidney injury. Although UMOD has been found for over 60 years, its new functions are constantly being discovered. UMOD has been recognized as an important regulatory protein of innate immune via binding complement fragments. [1][2][3][4][5][6] Our previous study has shown that UMOD can bind complement factor H (cFH) and enhance its ability as a cofactor of complement factor I to degenerate C3b. 7 UMOD is expressed and secreted by epithelial cell on thick ascending limb (TAL) of Henle's loop and early distal convoluted tubules (DCT) of the nephron, 8 which are important functional segments of renal tubules. 7,9,10 There are gradient changes of pH and ion concentration in this part under physiological and pathological status, 11,12 and the epithelial cells in the region are sensitive to the changes of pH and
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