Universität zu Köln

Hermert, Daniela, Martin, Ina, V, Reiss, Lucy K., Liu, Xiyang, Breitkopf, Daniel M., Reimer, Katharina C., Alidousty, Christina, Rauen, Thomas, Floege, Juergen, Ostendorf, Tammo, Weiskirchen, Ralf ORCID: 0000-0003-3888-0931 and Raffetseder, Ute (2020). The nucleic acid binding protein YB-1-controlled expression of CXCL-1 modulates kidney damage in liver fibrosis. Kidney Int., 97 (4). S. 741 - 753. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1755

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Abstract

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 Cxc/1 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hermert, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Martin, Ina, V UNSPECIFIED UNSPECIFIED UNSPECIFIED Reiss, Lucy K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Liu, Xiyang UNSPECIFIED UNSPECIFIED UNSPECIFIED Breitkopf, Daniel M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reimer, Katharina C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Alidousty, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Rauen, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Floege, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Ostendorf, Tammo UNSPECIFIED UNSPECIFIED UNSPECIFIED Weiskirchen, Ralf UNSPECIFIED orcid.org/0000-0003-3888-0931 UNSPECIFIED Raffetseder, Ute UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-339660
DOI:	10.1016/j.kint.2019.10.024
Journal or Publication Title:	Kidney Int.
Volume:	97
Number:	4
Page Range:	S. 741 - 753
Date:	2020
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1523-1755
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Y-BOX PROTEIN-1; CCL5 EXPRESSION; TRANSCRIPTION FACTOR; RENAL DYSFUNCTION; YB-1; INFLAMMATION; RECEPTOR; INJURY; CXCR2; CHEMOKINES Multiple languages Urology & Nephrology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33966