YB-1 increases glomerular, but decreases interstitial fibrosis in CNI-induced nephropathy

YB-1 increases glomerular, but decreases interstitial fibrosis in CNI-induced nephropathy

Copyright © 2018 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 194(2018) vom: 25. Sept., Seite 67-74
1. Verfasser: Gibbert, Lydia (VerfasserIn)
Weitere Verfasser: Hermert, Daniela, Wang, Jialin, M Breitkopf, Daniel, Alidousty, Christina, Neusser, Matthias, Cohen, Clemens D, Gröne, Elisabeth, Macheleidt, Iris, Rauen, Thomas, Braun, Gerald S, Floege, Jürgen, Ostendorf, Tammo, Raffetseder, Ute
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2018
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't CNI-induced nephropathy Calcineurin inhibitor Renal fibrosis Subcellular shuttling YB-1 Calcineurin Inhibitors Transcription Factors YB-1 protein, mouse
Beschreibung
Zusammenfassung:Copyright © 2018 Elsevier Inc. All rights reserved.
Calcineurin inhibitors (CNIs) are a cornerstone of the current treatment in solid organ transplantation and autoimmune disease. However, CNIs also bear deleterious effects as they cause glomerular and tubulointerstitial fibrosis in the kidney. We recently identified Y-box protein-1 (YB-1) as a novel downstream effector of CNI-signaling in the cytoplasm of glomerular cells. In the present study, we corroborate the pro-fibrotic role of YB-1 in glomeruli of patients under CNI-treatment. Such effects in glomeruli are significantly mitigated in CNI-treated mice with half-normal YB-1 expression (Yb1+/-). Surprisingly, in the tubulointerstitium we observe an opposite role of the CNI-YB-1 axis. Here, YB-1 is predominantly located to the nuclei and represses transcription of several extracellular matrix genes. Consistently, CNI-treatment in Yb1+/- mice markedly increases pro-fibrotic changes in the tubulointerstitium. In summary, our data provide evidence that fibrotic CNI-induced YB-1 effects in glomerular cells need to be contrasted with beneficial anti-fibrotic effects in the tubulointerstitium
Beschreibung:Date Completed 14.08.2019
Date Revised 14.08.2019
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2018.07.002