Abstract
The number of B cells is increased and the O-glycans of IgA1 are incompletely galactosylated in IgA nephropathy (IgAN). Here we report that expression of phosphatase and tensin homolog (PTEN) and Cosmc is decreased in B cells, and correlates with B cell number and the aberrant glycosylation of IgA1 in IgAN. Patients with IgAN exhibit higher miR-374b in B cells compared to controls. We show that miR-374b targets PTEN and Cosmc by luciferase assays and western blot analysis. Inhibition of miR-374b increased PTEN and Cosmc expression, and prevented cell proliferation and aberrant glycosylation of IgA1, thus representing a new therapeutic approach for IgAN.
Keywords:
B cell; IgA nephropathy; MiR-374b.
Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions
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Adult
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism*
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B-Lymphocytes / pathology
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Cell Line, Tumor
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Cell Proliferation
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Cells, Cultured
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Female
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Glomerulonephritis, IGA / immunology
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Glomerulonephritis, IGA / metabolism*
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Glomerulonephritis, IGA / pathology
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Glycosylation
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Humans
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Immunoglobulin A / metabolism*
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Male
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / metabolism*
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Middle Aged
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Molecular Chaperones / antagonists & inhibitors*
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Molecular Chaperones / genetics
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Molecular Chaperones / metabolism
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PTEN Phosphohydrolase / antagonists & inhibitors*
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PTEN Phosphohydrolase / genetics
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PTEN Phosphohydrolase / metabolism
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RNA / metabolism
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RNA Interference
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Young Adult
Substances
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3' Untranslated Regions
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C1GALT1C1 protein, human
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Immunoglobulin A
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MIRN374 microRNA 374, human
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MicroRNAs
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Molecular Chaperones
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RNA, recombinant
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Recombinant Proteins
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RNA
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PTEN Phosphohydrolase
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PTEN protein, human