title: Impact of feline AIM on the susceptibility of cats to renal disease.
abstract: Renal failure is one of the most important social problems for its incurability and high costs for patients' health care. Through clarification of the underlying mechanism for the high susceptibility of cats to renal disease, we here demonstrates that the effective dissociation of serum AIM protein from IgM is necessary for the recovery from acute kidney injury (AKI). In cats, the AIM-IgM binding affinity is 1000-fold higher than that in mice, which is caused by the unique positively-charged amino-acid cluster present in feline AIM. Hence, feline AIM does not dissociate from IgM during AKI, abolishing its translocation into urine. This results in inefficient clearance of lumen-obstructing necrotic cell debris at proximal tubules, thereby impairing AKI recovery. Accordingly, mice whose AIM is replaced by feline AIM exhibit higher mortality by AKI than in wild-type mice. Recombinant AIM administration into the mice improves their renal function and survival. As insufficient recovery from AKI predisposes patients to chronic, end-stage renal disease, feline AIM may be involved crucially in the high mortality of cats due to renal disease. Our findings could be the basis of the development of novel AKI therapies targeting AIM-IgM dissociation, and may support renal function in cats and prolong their lives.
authors.affiliation: Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Sugisawa
authors.affiliation: Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Emiri
authors.initials: E
authors.lastname: Hiramoto
authors.affiliation: Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.|Graduate School of Science, Osaka University, Osaka 560-0043, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Matsuoka
authors.affiliation: Laboratory of Small Animal Surgery 2, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Iwai
authors.affiliation: Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takai
authors.affiliation: Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamazaki
authors.affiliation: Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.|Department of Basic Veterinary Medicine, School of Veterinary Medicine, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Mori
authors.affiliation: Center of Advanced Studies in Veterinary Medicine, School of Veterinary Medicine, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Center for Animal Resources and Development, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takeda
authors.affiliation: Center for Animal Resources and Development, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Yamamura
authors.affiliation: Department of Basic Veterinary Medicine, School of Veterinary Medicine, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Arai
authors.affiliation: Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Arai
authors.affiliation: Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.|AMED-CREST, Japan Agency for Medical Research and Development, Tokyo 113-0033, Japan.|Max Planck-The University of Tokyo Center for Integrative Inflammology, Tokyo 113-0033, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Miyazaki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000737:chemistry*; D002371:Cat Diseases / Q000209:etiology*; D002415:Cats; D004198:Disease Susceptibility; D007674:Kidney Diseases / Q000662:veterinary*; D037181:Lectins, C-Type / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D000099192:CD69 Antigens