{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T13:13:43Z","timestamp":1781788423742,"version":"3.54.5"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,3,18]],"date-time":"2023-03-18T00:00:00Z","timestamp":1679097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"JSPS KAKENHI"},{"name":"Joint Usage\/Research Center Institute for Genetic Medicine, Hokkaido University"},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP223fa627005"],"award-info":[{"award-number":["JP223fa627005"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Using a zoobiquity concept, we directly connect animal phenotypes to a human disease mechanism: the reduction of local plasminogen levels caused by matrix metalloproteinase-9 (MMP9) activity is associated with the development of inflammation in the intestines of dogs and patients with inflammatory bowel disease. We first investigated inflammatory colorectal polyps (ICRPs), which are a canine gastrointestinal disease characterized by the presence of idiopathic chronic inflammation, in Miniature Dachshund (MD) and found 31 missense disease-associated SNPs by whole-exome sequencing. We sequenced them in 10 other dog breeds and found five, PLG, TCOF1, TG, COL9A2 and COL4A4, only in MD. We then investigated two rare and breed-specific missense SNPs (T\/T SNPs), PLG: c.477G &amp;gt; T and c.478A&amp;gt;T, and found that ICRPs with the T\/T SNP risk alleles showed less intact plasminogen and plasmin activity in the lesions compared to ICRPs without the risk alleles but no differences in serum. Moreover, we show that MMP9, which is an NF-\u03baB target, caused the plasminogen reduction and that intestinal epithelial cells expressing plasminogen molecules were co-localized with epithelial cells expressing MMP9 in normal colons with the risk alleles. Importantly, MMP9 expression in patients with ulcerous colitis or Crohn\u2019s disease also co-localized with epithelial cells showing enhanced NF-\u03baB activation and less plasminogen expression. Overall, our zoobiquity experiments showed that MMP9 induces the plasminogen reduction in the intestine, contributing to the development of local inflammation and suggesting the local MMP9-plasminogen axis is a therapeutic target in both dogs and patients. Therefore, zoobiquity-type experiments could bring new perspectives for biomarkers and therapeutic targets.<\/jats:p>","DOI":"10.1093\/intimm\/dxad006","type":"journal-article","created":{"date-parts":[[2023,3,18]],"date-time":"2023-03-18T17:05:37Z","timestamp":1679159137000},"page":"313-326","source":"Crossref","is-referenced-by-count":5,"title":["Zoobiquity experiments show the importance of the local MMP9-plasminogen axis in inflammatory bowel diseases in both dogs and patients"],"prefix":"10.1093","volume":"35","author":[{"given":"Takeshi","family":"Yamasaki","sequence":"first","affiliation":[{"name":"Division of Molecular Psychoimmunology, Institute for Genetic Medicine, Graduate School of Medicine, Hokkaido University , Sapporo , Japan"},{"name":"Division of Molecular Neuroimmunology, National Institute for Physiological Sciences, National Institute of Natural Sciences , Okazaki , 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