Experimental cell research, 2015-04, Vol.333 (1), p.155-163
2015
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- Autor(en) / Beteiligte
- Titel
- MicroRNA-10b downregulation mediates acute rejection of renal allografts by derepressing BCL2L11
- Ist Teil von
- Experimental cell research, 2015-04, Vol.333 (1), p.155-163
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. •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.•miR-10b downregulation derepressed its pro-apoptotic target BCL2L11.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0014-4827eISSN: 1090-2422DOI: 10.1016/j.yexcr.2015.01.018Titel-ID: cdi_osti_scitechconnect_22462277
- Format
- –
- Schlagworte
- 60 APPLIED LIFE SCIENCES, Acute renal allograft rejection, Allografts, APOPTOSIS, Apoptosis Regulatory Proteins - genetics, Apoptosis Regulatory Proteins - metabolism, Base Sequence, Bcl-2-Like Protein 11, BCL2L11, Binding Sites, Case-Control Studies, Cells, Cultured, Cellular biology, Chemokines - secretion, Chemotaxis, Down-Regulation, Endothelial cells, Graft Rejection - genetics, Graft Rejection - immunology, Graft Rejection - metabolism, Humans, INFLAMMATION, Inflammatory cytokines, INTERFERON, Kidney diseases, Kidney Transplantation, KIDNEYS, LIGANDS, LUCIFERASE, MACROPHAGES, Macrophages - physiology, Membrane Proteins - genetics, Membrane Proteins - metabolism, microRNA, MicroRNAs, MicroRNAs - genetics, MicroRNAs - metabolism, PATIENTS, Proto-Oncogene Proteins - genetics, Proto-Oncogene Proteins - metabolism, RADIOPROTECTIVE SUBSTANCES, RNA Interference, Transplants & implants