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Nat Med. 2016 Feb;22(2):183-93. doi: 10.1038/nm.4012. Epub 2016 Jan 4.

Apoptosis inhibitor of macrophage protein enhances intraluminal debris clearance and ameliorates acute kidney injury in mice.

Author information

1
Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
2
Matthew Mailing Centre for Translational Transplant Studies, Lawson Health Research Institute, London, Ontario, Canada.
3
Department of Emergency and Critical Care Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
4
Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
5
Department of Nephrology and Endocrinology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
6
Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
7
Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
8
Division of Nephrology, Department of Medicine, McGill University Health Centre, McGill University, Quebec, Canada.
9
Agency for Medical Research and Development-Core Research for Evolutional Medical Science and Technology (AMED-CREST), Japan Agency for Medical Research and Development, Tokyo, Japan.
10
Max Planck-The University of Tokyo Center for Integrative Inflammology, Tokyo, Japan.

Abstract

Acute kidney injury (AKI) is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been established. Here we show that the apoptosis inhibitor of macrophage (AIM) protein on intraluminal debris interacts with kidney injury molecule (KIM)-1 and promotes recovery from AKI. During AKI, the concentration of AIM increases in the urine, and AIM accumulates on necrotic cell debris within the kidney proximal tubules. The AIM present in this cellular debris binds to KIM-1, which is expressed on injured tubular epithelial cells, and enhances the phagocytic removal of the debris by the epithelial cells, thus contributing to kidney tissue repair. When subjected to ischemia-reperfusion (IR)-induced AKI, AIM-deficient mice exhibited abrogated debris clearance and persistent renal inflammation, resulting in higher mortality than wild-type (WT) mice due to progressive renal dysfunction. Treatment of mice with IR-induced AKI using recombinant AIM resulted in the removal of the debris, thereby ameliorating renal pathology. We observed this effect in both AIM-deficient and WT mice, but not in KIM-1-deficient mice. Our findings provide a basis for the development of potentially novel therapies for AKI.

PMID:
26726878
DOI:
10.1038/nm.4012
[Indexed for MEDLINE]

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