Universität zu Köln

Heinemann, Falko M., Jindra, Peter T., Bockmeyer, Clemens L., Zeuschner, Philip ORCID: 0000-0001-8898-6588, Wittig, Juliane, Hoeflich, Heike, Esser, Marc, Abbas, Mahmoud, Dieplinger, Georg, Stolle, Katharina, Vester, Udo, Hoyer, Peter F., Immenschuh, Stephan ORCID: 0000-0003-3722-5791, Heinold, Andreas, Horn, Peter A., Li, Wentian ORCID: 0000-0003-1155-110X, Eisenberger, Ute and Becker, Jan U. (2017). Glomerulocapillary miRNA response to HLA-class I antibody in vitro and in vivo. Sci Rep, 7. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Heinemann, Falko M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jindra, Peter T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bockmeyer, Clemens L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zeuschner, Philip UNSPECIFIED orcid.org/0000-0001-8898-6588 UNSPECIFIED Wittig, Juliane UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoeflich, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Esser, Marc UNSPECIFIED UNSPECIFIED UNSPECIFIED Abbas, Mahmoud UNSPECIFIED UNSPECIFIED UNSPECIFIED Dieplinger, Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Stolle, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Vester, Udo UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoyer, Peter F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Immenschuh, Stephan UNSPECIFIED orcid.org/0000-0003-3722-5791 UNSPECIFIED Heinold, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Horn, Peter A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Wentian UNSPECIFIED orcid.org/0000-0003-1155-110X UNSPECIFIED Eisenberger, Ute UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Jan U. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-211475
DOI:	10.1038/s41598-017-14674-5
Journal or Publication Title:	Sci Rep
Volume:	7
Date:	2017
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MATRIX-METALLOPROTEINASE 2; LET-7 MICRORNA BIOGENESIS; BCL-XL EXPRESSION; ENDOTHELIAL-CELLS; MEDIATED REJECTION; METASTASIS; ACTIVATION; INDUCTION; CANCER; GROWTH Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21147