Universität zu Köln

Li, Jinhong, Tang, Ying, Tang, Patrick M. K., Lv, Jun, Huang, Xiao-ru, Carlsson-Skwirut, Christine, Da Costa, Lydie, Aspesi, Anna, Froehlich, Suada, Szczesniak, Pawel, Lacher, Philipp, Klug, Joerg, Meinhardt, Andreas, Fingerle-Rowson, Guenter, Gong, Rujun, Zheng, Zhihua, Xu, Anping and Lan, Hui-yao (2018). Blocking Macrophage Migration Inhibitory Factor Protects Against Cisplatin-Induced Acute Kidney Injury in Mice. Mol. Ther., 26 (10). S. 2523 - 2533. CAMBRIDGE: CELL PRESS. ISSN 1525-0024

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Abstract

Macrophage migration inhibitory factor (MIF) is elevated in patients with acute kidney injury (AKI) and is suggested as a potential predictor for renal replacement therapy in AKI. In this study, we found that MIF also plays a pathogenic role and is a therapeutic target for AKI. In a cisplatin-induced AKI mouse model, elevated plasma MIF correlated with increased serum creatinine and the severity of renal inflammation and tubular necrosis, whereas deletion of MIF protected the kidney from cisplatin-induced AKI by largely improving renal functional and histological injury, and suppressing renal inflammation including upregulation of cytokines such as interleukin (IL)-1 beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, inducible nitric oxide synthase (iNOS), MCP-1, IL-8, and infiltration of macrophages, neutrophils, and T cells. We next developed a novel therapeutic strategy for AKI by blocking the endogenous MIF with an MIF inhibitor, ribosomal protein S19 (RPS19). Similar to the MIF-knockout mice, treatment with RPS19, but not the mutant RPS19, suppressed cisplatin-induced AKI. Mechanistically, we found that both genetic knockout and pharmacological inhibition of MIF protected against AKI by inactivating the CD74-nuclear factor kappa B (NF-kappa B) signaling. In conclusion, MIF is pathogenic in cisplatin-induced AKI. Targeting MIF with an MIF inhibitor RPS19 could be a promising therapeutic potential for AKI.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Li, Jinhong UNSPECIFIED UNSPECIFIED UNSPECIFIED Tang, Ying UNSPECIFIED UNSPECIFIED UNSPECIFIED Tang, Patrick M. K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lv, Jun UNSPECIFIED UNSPECIFIED UNSPECIFIED Huang, Xiao-ru UNSPECIFIED UNSPECIFIED UNSPECIFIED Carlsson-Skwirut, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Da Costa, Lydie UNSPECIFIED UNSPECIFIED UNSPECIFIED Aspesi, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Froehlich, Suada UNSPECIFIED UNSPECIFIED UNSPECIFIED Szczesniak, Pawel UNSPECIFIED UNSPECIFIED UNSPECIFIED Lacher, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Klug, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Meinhardt, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Fingerle-Rowson, Guenter UNSPECIFIED UNSPECIFIED UNSPECIFIED Gong, Rujun UNSPECIFIED UNSPECIFIED UNSPECIFIED Zheng, Zhihua UNSPECIFIED UNSPECIFIED UNSPECIFIED Xu, Anping UNSPECIFIED UNSPECIFIED UNSPECIFIED Lan, Hui-yao UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-169600
DOI:	10.1016/j.ymthe.2018.07.014
Journal or Publication Title:	Mol. Ther.
Volume:	26
Number:	10
Page Range:	S. 2523 - 2533
Date:	2018
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1525-0024
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FACTOR MIF; TNF-ALPHA; INFLAMMATION; EXPRESSION; CELLS; NEPHROTOXICITY; INVOLVEMENT; ACTIVATION; DISEASE; S19 Multiple languages Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16960