The nucleic acid binding protein YB-1-controlled expression of CXCL-1 modulates kidney damage in liver fibrosis.

Autor:	Hermert D; Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany., Martin IV; Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany., Reiss LK; Institute of Pharmacology and Toxicology, Medical Faculty, RWTH-Aachen University, Aachen, Germany., Liu X; Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany., Breitkopf DM; Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany., Reimer KC; Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany., Alidousty C; Department of Pathology, University Hospital of Cologne, Cologne, Germany., Rauen T; Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany., Floege J; Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany., Ostendorf T; Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany., Weiskirchen R; Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), University Hospital RWTH-Aachen, Aachen, Germany., Raffetseder U; Department of Nephrology and Clinical Immunology, University Hospital RWTH-Aachen, Aachen, Germany. Electronic address: uraffetseder@ukaachen.de.
Jazyk:	angličtina
Zdroj:	Kidney international [Kidney Int] 2020 Apr; Vol. 97 (4), pp. 741-752. Date of Electronic Publication: 2019 Nov 09.
DOI:	10.1016/j.kint.2019.10.024
Abstrakt:	Acute kidney injury is a common complication of advanced liver disease and increased mortality of these patients. Here, we analyzed the role of Y-box protein-1 (YB-1), a nucleic acid binding protein, in the bile duct ligation model of liver fibrosis and monitored liver and subsequent kidney damage. Following bile duct ligation, both serum levels of liver enzymes and expression of hepatic extracellular matrix components such as type I collagen were significantly reduced in mice with half-maximal YB-1 expression (Yb1 +/- ) as compared to their wild-type littermates. By contrast, expression of the chemokine CXCL1 was significantly augmented in these Yb1 +/- mice. YB-1 was identified as a potent transcriptional repressor of the Cxcl1 gene. Precision-cut kidney slices from Yb1 +/- mice revealed higher expression of the CXCL1 receptor CXCR2 as well as enhanced responsivity to CXCL1 compared to those from wild-type mice. Increased CXCL1 content in Yb1 +/- mice led to pronounced bile duct ligation-induced damage of the kidneys monitored as parameters of tubular epithelial injury and immune cell infiltration. Pharmacological blockade of CXCR2 as well as application of an inhibitory anti-CXCL1 antibody significantly mitigated early systemic effects on the kidneys following bile duct ligation whereas it had only a modest impact on hepatic inflammation and function. Thus, our analyses provide direct evidence that YB-1 crucially contributes to hepatic fibrosis and modulates liver-kidney crosstalk by maintaining tight control over chemokine CXCL1 expression. (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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