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Exp Cell Res. 2015 Apr 10;333(1):155-63. doi: 10.1016/j.yexcr.2015.01.018. Epub 2015 Feb 7.

MicroRNA-10b downregulation mediates acute rejection of renal allografts by derepressing BCL2L11.

Author information

1
Department of Organ Transplantation, Zhujiang Hospital, Guangzhou 510282, China.
2
Institute of Molecular Ecology and Evolution, East China Normal University, Shanghai 200062, China.
3
Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China; State Key Laboratory of Digestive Diseases, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
4
Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
5
Guangxi Key Laboratory for Transplantation Medicine Department of Organ Transplantation in Guangzhou Military Region, Institute of Transplant Medicine, 303 Hospital of People׳s Liberation Army, Nanning, Guangxi 530021, China.
6
Guangxi Key Laboratory for Transplantation Medicine Department of Organ Transplantation in Guangzhou Military Region, Institute of Transplant Medicine, 303 Hospital of People׳s Liberation Army, Nanning, Guangxi 530021, China. Electronic address: sunxuyong0528@163.com.

Abstract

Kidney transplantation is the major therapeutic option for end-stage kidney diseases. However, acute rejection could cause allograft loss in some of these patients. Emerging evidence supports that microRNA (miRNA) dysregulation is implicated in acute allograft rejection. In this study, we used next-generation sequencing to profile miRNA expression in normal and acutely rejected kidney allografts. Among 75 identified dysregulated miRNAs, miR-10b was the most significantly downregulated miRNAs in rejected allografts. Transfecting miR-10b inhibitor into human renal glomerular endothelial cells recapitulated key features of acute allograft rejection, including endothelial cell apoptosis, release of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor α, interferon-γ, and chemokine (C-C motif) ligand 2) and chemotaxis of macrophages whereas transfection of miR-10b mimics had opposite effects. Downregulation of miR-10b directly derepressed the expression of BCL2L11 (an apoptosis inducer) as revealed by luciferase reporter assay. Taken together, miR-10b downregulation mediates many aspects of disease pathogenicity of acute kidney allograft rejection. Restoring miR-10b expression in glomerular endothelial cells could be a novel therapeutic approach to reduce acute renal allograft loss.

KEYWORDS:

Acute renal allograft rejection; BCL2L11; Endothelial cells; Inflammatory cytokines; microRNA

PMID:
25659925
DOI:
10.1016/j.yexcr.2015.01.018
[Indexed for MEDLINE]

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