Increased miR-374b promotes cell proliferation and the production of aberrant glycosylated IgA1 in B cells of IgA nephropathy

Shuai Hu; Hao Bao; Xiaodong Xu; Xianguang Zhou; Weisong Qin; Caihong Zeng; Zhihong Liu

doi:10.1016/j.febslet.2015.10.033

Increased miR-374b promotes cell proliferation and the production of aberrant glycosylated IgA1 in B cells of IgA nephropathy

FEBS Lett. 2015 Dec 21;589(24 Pt B):4019-25. doi: 10.1016/j.febslet.2015.10.033. Epub 2015 Nov 9.

Authors

Shuai Hu¹, Hao Bao², Xiaodong Xu¹, Xianguang Zhou¹, Weisong Qin¹, Caihong Zeng¹, Zhihong Liu³

Affiliations

¹ National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
² National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China. Electronic address: bhao@nju.edu.cn.
³ National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China. Electronic address: liuzhihong@nju.edu.cn.

PMID: 26545495
DOI: 10.1016/j.febslet.2015.10.033

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions
Adult
B-Lymphocytes / immunology
B-Lymphocytes / metabolism*
B-Lymphocytes / pathology
Cell Line, Tumor
Cell Proliferation
Cells, Cultured
Female
Glomerulonephritis, IGA / immunology
Glomerulonephritis, IGA / metabolism*
Glomerulonephritis, IGA / pathology
Glycosylation
Humans
Immunoglobulin A / metabolism*
Male
MicroRNAs / antagonists & inhibitors
MicroRNAs / metabolism*
Middle Aged
Molecular Chaperones / antagonists & inhibitors*
Molecular Chaperones / genetics
Molecular Chaperones / metabolism
PTEN Phosphohydrolase / antagonists & inhibitors*
PTEN Phosphohydrolase / genetics
PTEN Phosphohydrolase / metabolism
RNA / metabolism
RNA Interference
Recombinant Proteins / chemistry
Recombinant Proteins / metabolism
Young Adult

Substances

3' Untranslated Regions
C1GALT1C1 protein, human
Immunoglobulin A
MIRN374 microRNA 374, human
MicroRNAs
Molecular Chaperones
RNA, recombinant
Recombinant Proteins
RNA
PTEN Phosphohydrolase
PTEN protein, human