Pathophysiological contributions of fucosyltransferases in renal ischemia reperfusion injury.
Ischemia reperfusion injury (IRI) is a major cause of delayed graft function. Recent studies have shown that selectins play an important role in IRI. Selectins bind to sialylated and fucosylated sLe(x) receptors, and two enzymes, fucosyltransferase IV (FucT-IV) and VII (FucT-VII), are important in the function of these receptors. We hypothesized that fucosyltransferase (FucT) enzymes were important pathophysiologic mediators of renal IRI. We therefore evaluated renal IRI in mice deficient in FucT-IV, FucT-VII, and both FucT-IV and FucT-VII and compared their renal function, tubular injury, selectin ligand expression, and neutrophil infiltration to those in wild-type control mice. Bilateral 30-min renal IRI was performed, and the results demonstrated that mice deficient in both FucT-IV/FucT-VII were significantly protected from renal IRI at 24 and 48 h compared with wild-type control mice. FucT-IV-deficient mice showed only modest protection from renal injury at 24 h. However, FucT-VII-deficient mice had similar injury as wild-type mice. Histological analysis of kidney tissue postischemia revealed that mice deficient in both FucT-IV and FucT-VII had significantly reduced tubular injury compared with wild-type mice. Selectin ligand expression increased postischemia in wild-type, but not FucT-IV/FucT-VII-deficient, mice. Neutrophil infiltration in postischemic kidneys of FucT-IV/FucT-VII-deficient mice was also attenuated. These data demonstrate that fucosyltransferases are important in the pathogenesis of renal IRI and are potential therapeutic targets.
Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Melissa J
MJ
Burne
Hamid
H
Rabb
D000818:Animals; D003404:Creatinine / Q000097:blood; D019040:E-Selectin / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D005647:Fucosyltransferases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007075:Immunoglobulin M / Q000235:genetics; D007668:Kidney / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D007677:Kidney Function Tests; D007683:Kidney Tubular Necrosis, Acute / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000235:genetics; D009504:Neutrophils / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000032:analysis; D015427:Reperfusion Injury / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D013194:Staining and Labeling
D019040:E-Selectin; D007075:Immunoglobulin M; D011993:Recombinant Fusion Proteins; D003404:Creatinine; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase