skip to main content

SciTech ConnectSciTech Connect

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

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. - Highlights: • miR-10b was the most downregulated microRNAs in acutely rejected renal allografts. • miR-10b downregulation triggered glomerular endothelial cell apoptosis. • miR-10b downregulation induced release of pro-inflammatory cytokines. •more » miR-10b downregulation derepressed its pro-apoptotic target BCL2L11.« less
Authors:
 [1] ;  [2] ;  [1] ;  [3] ;  [4] ;  [3] ;  [1] ; ;  [5] ;  [5]
  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)
  4. (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)
Publication Date:
OSTI Identifier:
22462277
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 333; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; INFLAMMATION; INTERFERON; KIDNEYS; LIGANDS; LUCIFERASE; MACROPHAGES; PATIENTS; RADIOPROTECTIVE SUBSTANCES