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Identification of cell and disease specific microRNAs in glomerular pathologies

Journal article
Authors J. Muller-Deile
J. Dannenberg
Peidi Liu
J. Lorenzen
Jenny Nyström
T. Thum
M. Schiffer
Published in Journal of Cellular and Molecular Medicine
Volume 23
Issue 6
Pages 3927-3939
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Physiology
Pages 3927-3939
Language en
Links dx.doi.org/10.1111/jcmm.14270
Keywords diagnostic marker, glomerular diseases, microRNA-screening, renal cells, urine, expression, contributes, survival, deletion, barrier, urine, rnas, Cell Biology, Research & Experimental Medicine, ates of america, v105, p10513, actice, v888, p253
Subject categories Clinical Laboratory Medicine

Abstract

MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression in physiological processes as well as in diseases. Currently miRs are already used to find novel mechanisms involved in diseases and in the future, they might serve as diagnostic markers. To identify miRs that play a role in glomerular diseases urinary miR-screenings are a frequently used tool. However, miRs that are detected in the urine might simply be filtered from the blood stream and could have been produced anywhere in the body, so they might be completely unrelated to the diseases. We performed a combined miR-screening in pooled urine samples from patients with different glomerular diseases as well as in cultured human podocytes, human mesangial cells, human glomerular endothelial cells and human tubular cells. The miR-screening in renal cells was done in untreated conditions and after stimulation with TGF-beta. A merge of the detected regulated miRs led us to identify disease-specific, cell type-specific and cell stress-induced miRs. Most miRs were down-regulated following the stimulation with TGF-beta in all cell types. Up-regulation of miRs after TGF-beta was cell type-specific for most miRs. Furthermore, urinary miRs from patients with different glomerular diseases could be assigned to the different renal cell types. Most miRs were specifically regulated in one disease. Only miR-155 was up-regulated in all disease urines compared to control and therefore seems to be rather unspecific. In conclusion, a combined urinary and cell miR-screening can improve the interpretation of screening results. These data are useful to identify novel miRs potentially involved in glomerular diseases.

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