{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T07:51:45Z","timestamp":1773906705644,"version":"3.50.1"},"reference-count":62,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Japan Society for Promotion of Sciences","award":["21H02695, 21K09317, 20K07323, and 18K06889"],"award-info":[{"award-number":["21H02695, 21K09317, 20K07323, and 18K06889"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-enzymatic glycation is an unavoidable reaction that occurs across biological taxa. The final products of this irreversible reaction are called advanced glycation end-products (AGEs). The endogenously formed AGEs are known to be bioactive and detrimental to human health. Additionally, exogenous food-derived AGEs are debated to contribute to the development of aging and various diseases. Receptor for AGEs (RAGE) is widely known to elicit biological reactions. The binding of RAGE to other ligands (e.g., high mobility group box 1, S100 proteins, lipopolysaccharides, and amyloid-\u03b2) can result in pathological processes via the activation of intracellular RAGE signaling pathways, including inflammation, diabetes, aging, cancer growth, and metastasis. RAGE is now recognized as a pattern-recognition receptor. All mammals have RAGE homologs; however, other vertebrates, such as birds, amphibians, fish, and reptiles, do not have RAGE at the genomic level. This evidence from an evolutionary perspective allows us to understand why mammals require RAGE. In this review, we provide an overview of the scientific knowledge about the role of RAGE in physiological and pathological processes. In particular, we focus on (1) RAGE biology, (2) the role of RAGE in physiological and pathophysiological processes, (3) RAGE isoforms, including full-length membrane-bound RAGE (mRAGE), and the soluble forms of RAGE (sRAGE), which comprise endogenous secretory RAGE (esRAGE) and an ectodomain-shed form of RAGE, and (4) oxytocin transporters in the brain and intestine, which are important for maternal bonding and social behaviors.<\/jats:p>","DOI":"10.3390\/ijms23042086","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T20:26:42Z","timestamp":1644870402000},"page":"2086","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Dual Nature of RAGE in Host Reaction and Nurturing the Mother\u2013Infant Bond"],"prefix":"10.3390","volume":"23","author":[{"given":"Yu","family":"Oshima","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ai","family":"Harashima","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiichi","family":"Munesue","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumi","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1927-0855","authenticated-orcid":false,"given":"Nontaphat","family":"Leerach","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisanori","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariko","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akane","family":"Niimura","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenjiro","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"},{"name":"Komatsu University, Komatsu 923-0921, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1779-0606","authenticated-orcid":false,"given":"Haruhiro","family":"Higashida","sequence":"additional","affiliation":[{"name":"Department of Basic Research on Social Recognition and Memory, Research Center for Child Mental Development, Kanazawa University, Kanazawa 920-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1326-4649","authenticated-orcid":false,"given":"Yasuhiko","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101920","DOI":"10.1016\/j.redox.2021.101920","article-title":"Protein glycation\u2014Biomarkers of metabolic dysfunction and early-stage decline in health in the era of precision medicine","volume":"42","author":"Rabbani","year":"2021","journal-title":"Redox Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/j.2040-1124.2011.00191.x","article-title":"Controlling the receptor for advanced glycation end-products to conquer diabetic vascular complications","volume":"3","author":"Yamamoto","year":"2012","journal-title":"J. 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