PMID- 29109529 OWN - NLM STAT- MEDLINE DCOM- 20190705 LR - 20240314 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 IP - 1 DP - 2017 Nov 6 TI - Glomerulocapillary miRNA response to HLA-class I antibody in vitro and in vivo. PG - 14554 LID - 10.1038/s41598-017-14674-5 [doi] LID - 14554 AB - Changes in miRNA expression glomerular of capillaries during antibody-mediated rejection (ABMR) are poorly understood and could contribute to the deleterious inflammation and fibrosis of ABMR via suppression of target genes. A better understanding could lead to novel diagnostic tools and reveal novel therapeutic targets. We explored deregulated miRNAs in an glomeruloendothelial in vitro model of ABMR due to class I human leukocyte antigen (HLA) with and without complement activation. We studied a set of 16 promising candidate miRNAs in microdissected glomeruli a confirmation set of 20 human transplant biopsies (DSA+) compared to 10 matched controls without evidence for ABMR. Twelve out of these 16 glomerulocapillary miRNAs could successfully be confirmed as dysregulated in vivo with 10 upregulated (let-7c-5p, miR-28-3p, miR-30d-5p, miR-99b-5p, miR-125a-5p, miR-195-5p, miR-374b-3p, miR-484, miR-501-3p, miR-520e) and 2 downregulated (miR29b-3p, miR-885-5p) in DSA+ vs. CONTROLS: A random forest analysis based on glomerular miRNAs identified 18/20 DSA+ and 8/10 controls correctly. This glomerulocapillary miRNA signature associated with HLA class I-DSA could improve our understanding of ABMR and be useful for diagnostic or therapeutic purposes. FAU - Heinemann, Falko M AU - Heinemann FM AD - Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany. FAU - Jindra, Peter T AU - Jindra PT AD - Immune Evaluation Laboratory, Department of Surgery, Baylor College of Medicine, Houston, TX, USA. FAU - Bockmeyer, Clemens L AU - Bockmeyer CL AD - Institute of Pathology, Department of Nephropathology, University Hospital Erlangen-Nurnberg, Erlangen, Germany. FAU - Zeuschner, Philip AU - Zeuschner P AD - Institute of Pathology, University Hospital of Cologne, Cologne, Germany. FAU - Wittig, Juliane AU - Wittig J AD - Institute of Pathology, University Hospital of Cologne, Cologne, Germany. FAU - Hoflich, Heike AU - Hoflich H AD - Institute of Pathology, Hannover Medical School, Hannover, Germany. FAU - Esser, Marc AU - Esser M AD - Institute of Pathology, University Hospital of Cologne, Cologne, Germany. FAU - Abbas, Mahmoud AU - Abbas M AD - PATHOCOM, Rheine, Germany. FAU - Dieplinger, Georg AU - Dieplinger G AD - Department of General, Visceral and Cancer Surgery, Transplant Center Cologne, University of Cologne, Cologne, Germany. FAU - Stolle, Katharina AU - Stolle K AD - Institute of Pathology, University Hospital of Cologne, Cologne, Germany. FAU - Vester, Udo AU - Vester U AD - Children's Hospital, Pediatrics II, University of Duisburg-Essen, Essen, Germany. FAU - Hoyer, Peter F AU - Hoyer PF AD - Children's Hospital, Pediatrics II, University of Duisburg-Essen, Essen, Germany. FAU - Immenschuh, Stephan AU - Immenschuh S AD - Institute of Transfusion Medicine, Hannover Medical School, Hannover, Germany. FAU - Heinold, Andreas AU - Heinold A AD - Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany. FAU - Horn, Peter A AU - Horn PA AD - Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany. FAU - Li, Wentian AU - Li W AUID- ORCID: 0000-0003-1155-110X AD - Robert S Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA. FAU - Eisenberger, Ute AU - Eisenberger U AD - Clinic for Nephrology, University Hospital Essen, University Duisburg-Essen, Essen, Germany. FAU - Becker, Jan U AU - Becker JU AD - Institute of Pathology, University Hospital of Cologne, Cologne, Germany. janbecker@gmx.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171106 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Autoantibodies) RN - 0 (HLA Antigens) RN - 0 (MicroRNAs) SB - IM EIN - Sci Rep. 2018 Apr 12;8(1):6003. PMID: 29651104 MH - Adult MH - Aged MH - Autoantibodies/*immunology MH - Capillaries/*metabolism MH - Female MH - Graft Rejection/immunology/metabolism MH - HLA Antigens/*immunology MH - Humans MH - In Vitro Techniques MH - Kidney Glomerulus/*blood supply/metabolism MH - Kidney Transplantation/adverse effects MH - Male MH - MicroRNAs/*metabolism MH - Middle Aged PMC - PMC5673998 COIS- The authors declare that they have no competing interests. EDAT- 2017/11/08 06:00 MHDA- 2019/07/06 06:00 PMCR- 2017/11/06 CRDT- 2017/11/08 06:00 PHST- 2017/02/15 00:00 [received] PHST- 2017/10/16 00:00 [accepted] PHST- 2017/11/08 06:00 [entrez] PHST- 2017/11/08 06:00 [pubmed] PHST- 2019/07/06 06:00 [medline] PHST- 2017/11/06 00:00 [pmc-release] AID - 10.1038/s41598-017-14674-5 [pii] AID - 14674 [pii] AID - 10.1038/s41598-017-14674-5 [doi] PST - epublish SO - Sci Rep. 2017 Nov 6;7(1):14554. doi: 10.1038/s41598-017-14674-5.