title: Abnormal miR-148b expression promotes aberrant glycosylation of IgA1 in IgA nephropathy.
abstract: Aberrant O-glycosylation in the hinge region of IgA1 characterizes IgA nephropathy. The mechanisms underlying this abnormal glycosylation are not well understood, but reduced expression of the enzyme core 1, β1,3-galactosyltransferase 1 (C1GALT1) may contribute. In this study, high-throughput microRNA (miRNA) profiling identified 37 miRNAs differentially expressed in PBMCs of patients with IgA nephropathy compared with healthy persons. Among them, we observed upregulation of miR-148b, which potentially targets C1GALT1. Patients with IgA nephropathy exhibited lower C1GALT1 expression, which negatively correlated with miR-148b expression. Transfection of PBMCs from healthy persons with a miR-148b mimic reduced endogenous C1GALT1 mRNA levels threefold. Conversely, loss of miR-148b function in PBMCs of patients with IgA nephropathy increased C1GALT1 mRNA and protein levels to those observed in healthy persons. Moreover, we found that upregulation of miR-148b directly correlated with levels of galactose-deficient IgA1. In vitro, we used an IgA1-producing cell line to confirm that miR-148b modulates IgA1 O-glycosylation and the levels of secreted galactose-deficient IgA1. Taken together, these data suggest a role for miRNAs in the pathogenesis of IgA nephropathy. Abnormal expression of miR-148b may explain the aberrant glycosylation of IgA1, providing a potential pharmacologic target for IgA nephropathy.
authors.affiliation: Nephrology Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Policlinico, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Serino
authors.forename: Fabio
authors.initials: F
authors.lastname: Sallustio
authors.forename: Sharon N
authors.initials: SN
authors.lastname: Cox
authors.forename: Francesco
authors.initials: F
authors.lastname: Pesce
authors.forename: Francesco P
authors.initials: FP
authors.lastname: Schena
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005700:Galactosyltransferases / Q000032:analysis / Q000235:genetics; D005922:Glomerulonephritis, IGA / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D007070:Immunoglobulin A; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; C505293:C1GALT1 protein, human; D005700:Galactosyltransferases