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

Clinical Immunology : the Official Journal of the Clinical Immunology Society
Lydia GibbertUte Raffetseder

Abstract

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.

Citations

Sep 5, 2019·Journal of Experimental & Clinical Cancer Research : CR·Yong WangDan Yue
Aug 8, 2019·Cell Communication and Signaling : CCS·Xiujuan ZhuJianhua Mao
Nov 5, 2021·Nature Reviews. Nephrology·Lisa SeufertRoman-Ulrich Müller

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