Impact of feline AIM on the susceptibility of cats to renal disease
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...
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| Veröffentlicht in: | Scientific reports 2016-10, Vol.6 (1), p.35251-35251, Article 35251 |
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| creator | Sugisawa, Ryoichi Hiramoto, Emiri Matsuoka, Shigeru Iwai, Satomi Takai, Ryosuke Yamazaki, Tomoko Mori, Nobuko Okada, Yuki Takeda, Naoki Yamamura, Ken-ichi Arai, Toshiro Arai, Satoko Miyazaki, Toru |
| description | 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. |
| doi_str_mv | 10.1038/srep35251 |
| format | Article |
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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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep35251</identifier><identifier>PMID: 27731392</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/1 ; 38 ; 38/77 ; 42 ; 59 ; 631/601/1737 ; 692/4022/1585 ; 82 ; 82/80 ; AIM protein ; End-stage renal disease ; Humanities and Social Sciences ; Immunoglobulin M ; Kidney diseases ; Kidney transplantation ; Mortality ; multidisciplinary ; Proximal tubules ; Renal failure ; Renal function ; Rodents ; Science ; Social conditions ; Translocation ; Urine</subject><ispartof>Scientific reports, 2016-10, Vol.6 (1), p.35251-35251, Article 35251</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Oct 2016</rights><rights>Copyright © 2016, The Author(s) 2016 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-90d5c433c82907e53cfc42ce27a28ecac54222015ced59d9e131ea5d909770ac3</citedby><cites>FETCH-LOGICAL-c504t-90d5c433c82907e53cfc42ce27a28ecac54222015ced59d9e131ea5d909770ac3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059666/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059666/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,41099,42168,51555,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27731392$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sugisawa, Ryoichi</creatorcontrib><creatorcontrib>Hiramoto, Emiri</creatorcontrib><creatorcontrib>Matsuoka, Shigeru</creatorcontrib><creatorcontrib>Iwai, Satomi</creatorcontrib><creatorcontrib>Takai, Ryosuke</creatorcontrib><creatorcontrib>Yamazaki, Tomoko</creatorcontrib><creatorcontrib>Mori, Nobuko</creatorcontrib><creatorcontrib>Okada, Yuki</creatorcontrib><creatorcontrib>Takeda, Naoki</creatorcontrib><creatorcontrib>Yamamura, Ken-ichi</creatorcontrib><creatorcontrib>Arai, Toshiro</creatorcontrib><creatorcontrib>Arai, Satoko</creatorcontrib><creatorcontrib>Miyazaki, Toru</creatorcontrib><title>Impact of feline AIM on the susceptibility of cats to renal disease</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>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.</description><subject>13</subject><subject>13/1</subject><subject>38</subject><subject>38/77</subject><subject>42</subject><subject>59</subject><subject>631/601/1737</subject><subject>692/4022/1585</subject><subject>82</subject><subject>82/80</subject><subject>AIM protein</subject><subject>End-stage renal disease</subject><subject>Humanities and Social Sciences</subject><subject>Immunoglobulin M</subject><subject>Kidney diseases</subject><subject>Kidney transplantation</subject><subject>Mortality</subject><subject>multidisciplinary</subject><subject>Proximal tubules</subject><subject>Renal failure</subject><subject>Renal function</subject><subject>Rodents</subject><subject>Science</subject><subject>Social 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Rep</addtitle><date>2016-10-12</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>35251</spage><epage>35251</epage><pages>35251-35251</pages><artnum>35251</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27731392</pmid><doi>10.1038/srep35251</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13 13/1 38 38/77 42 59 631/601/1737 692/4022/1585 82 82/80 AIM protein End-stage renal disease Humanities and Social Sciences Immunoglobulin M Kidney diseases Kidney transplantation Mortality multidisciplinary Proximal tubules Renal failure Renal function Rodents Science Social conditions Translocation Urine |
| title | Impact of feline AIM on the susceptibility of cats to renal disease |
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