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:
CreatorsEmailORCIDORCID Put Code
Li, JinhongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tang, YingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tang, Patrick M. K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lv, JunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huang, Xiao-ruUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carlsson-Skwirut, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Da Costa, LydieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aspesi, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Froehlich, SuadaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Szczesniak, PawelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lacher, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klug, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meinhardt, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fingerle-Rowson, GuenterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gong, RujunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zheng, ZhihuaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xu, AnpingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lan, Hui-yaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
FACTOR MIF; TNF-ALPHA; INFLAMMATION; EXPRESSION; CELLS; NEPHROTOXICITY; INVOLVEMENT; ACTIVATION; DISEASE; S19Multiple languages
Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & ExperimentalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16960

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