{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:56:13Z","timestamp":1790520973674,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Japan Society for the Promotion of Science","award":["18H02810"],"award-info":[{"award-number":["18H02810"]}]},{"name":"the Japan Society for the Promotion of Science","award":["924067"],"award-info":[{"award-number":["924067"]}]},{"name":"the Japan Society for the Promotion of Science","award":["18ek0109341h0001"],"award-info":[{"award-number":["18ek0109341h0001"]}]},{"name":"the Japan Science and Technology Agency","award":["18H02810"],"award-info":[{"award-number":["18H02810"]}]},{"name":"the Japan Science and Technology Agency","award":["924067"],"award-info":[{"award-number":["924067"]}]},{"name":"the Japan Science and Technology Agency","award":["18ek0109341h0001"],"award-info":[{"award-number":["18ek0109341h0001"]}]},{"name":"the Japan Agency for Medical Research and Development","award":["18H02810"],"award-info":[{"award-number":["18H02810"]}]},{"name":"the Japan Agency for Medical Research and Development","award":["924067"],"award-info":[{"award-number":["924067"]}]},{"name":"the Japan Agency for Medical Research and Development","award":["18ek0109341h0001"],"award-info":[{"award-number":["18ek0109341h0001"]}]},{"name":"Himuka AM Pharma, Ltd.","award":["18H02810"],"award-info":[{"award-number":["18H02810"]}]},{"name":"Himuka AM Pharma, Ltd.","award":["924067"],"award-info":[{"award-number":["924067"]}]},{"name":"Himuka AM Pharma, Ltd.","award":["18ek0109341h0001"],"award-info":[{"award-number":["18ek0109341h0001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Adrenomedullin (AM), a biologically active peptide, induces complete remission with mucosal healing in patients with refractory ulcerative colitis. We have developed 40 kDa PEGylated AM (PEG-AM), a long-acting AM derivative, as a potential therapeutic agent for inflammatory bowel disease (IBD). Both PEG-AM and native AM stimulated cyclic adenosine monophosphate (cAMP) production in HEK-293 cells stably expressing the AM1 receptor (CLR\/RAMP2 complex), in a dose-dependent manner. The pEC50 values for PEG-AM and AM were 7.23 \u00b1 0.05 and 8.42 \u00b1 0.10, respectively. PEG-AM exhibited significantly greater stability in plasma and serum than native AM. We evaluated the in vivo anti-colitis effects of intravenously administered PEG-AM in a dextran sodium sulfate (DSS)-induced murine colitis model. A single intravenous dose of PEG-AM, as low as 25 nmol\/kg, demonstrated therapeutic efficacy. Notably, AM receptor expression was not downregulated, despite sustained high plasma concentrations of PEG-AM. Additionally, PEG-AM exerted both therapeutic and preventive effects in a DSS colitis model. These findings suggest that PEG-AM is a promising therapeutic candidate for the treatment of patients with IBD.<\/jats:p>","DOI":"10.3390\/ijms26199373","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T12:48:28Z","timestamp":1758804508000},"page":"9373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In Vitro and In Vivo Characterization of 40 kDa PEGylated Adrenomedullin in a DSS-Induced Colitis Model"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5124-9549","authenticated-orcid":false,"given":"Kazuo","family":"Kitamura","sequence":"first","affiliation":[{"name":"Department of Project Research, Frontier Science Research Center, University of Miyazaki, Miyazaki 889-1692, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiko","family":"Akashi","sequence":"additional","affiliation":[{"name":"Department of Project Research, Frontier Science Research Center, University of Miyazaki, Miyazaki 889-1692, Japan"},{"name":"Department of Pharmacy, University of Miyazaki Hospital, Miyazaki 889-1692, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayaka","family":"Nagata","sequence":"additional","affiliation":[{"name":"Department of Project Research, Frontier Science Research Center, University of Miyazaki, Miyazaki 889-1692, Japan"},{"name":"Department of Food Science and Technology, Faculty of Health and Nutrition, Minami Kyushu University, Miyazaki 880-0032, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1903-9012","authenticated-orcid":false,"given":"Toshihiro","family":"Kita","sequence":"additional","affiliation":[{"name":"Department of Project Research, Frontier Science Research Center, University of Miyazaki, Miyazaki 889-1692, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoo","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Department of Project Research, Frontier Science Research Center, University of Miyazaki, Miyazaki 889-1692, Japan"},{"name":"Himuka AM Pharma Corp., Miyazaki 880-0812, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bretto, E., Urp\u00ec-Ferreruela, M., Casanova, G.R., and Gonz\u00e1lez-Su\u00e1rez, B. (2025). The Role of Gut Microbiota in Gastrointestinal Immune Homeostasis and Inflammation: Implications for Inflammatory Bowel Disease. Biomedicines, 13.","DOI":"10.3390\/biomedicines13081807"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"jjaf061","DOI":"10.1093\/ecco-jcc\/jjaf061","article-title":"Gene-Environment Interactions in Inflammatory Bowel Disease: A Systematic Review of Human Epidemiologic Studies","volume":"19","author":"Bai","year":"2025","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/s41575-025-01063-x","article-title":"Shaping the future of inflammatory bowel disease: A global research agenda for better management and public health response","volume":"22","author":"Solitano","year":"2025","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1080\/00365521.2025.2478166","article-title":"Temporal trends in characteristics and management of inflammatory bowel disease","volume":"60","author":"Young","year":"2025","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Maksic, M., Corovic, I., Maksic, T., Zivic, J., Zivic, M., Zdravkovic, N., Begovic, A., Medovic, M., Kralj, D., and Todorovic, Z. (2025). Molecular Insight into the Role of HLA Genotypes in Immunogenicity and Secondary Refractoriness to Anti-TNF Therapy in IBD Patients. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26157274"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1080\/17474124.2025.2468302","article-title":"The role of immunogenicity in optimizing biological therapies for inflammatory bowel disease","volume":"19","author":"Sharma","year":"2025","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1006\/bbrc.1993.1451","article-title":"Adrenomedullin: A novel hypotensive peptide isolated from human pheochromocytoma","volume":"192","author":"Kitamura","year":"1993","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0167-0115(99)00025-7","article-title":"Structure-activity relationships of adrenomedullin in the circulation and adrenal gland","volume":"85","author":"Champion","year":"1999","journal-title":"Regul. Pept."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1006\/bbrc.1996.0181","article-title":"Vasopressor activities of N-terminal fragments of adrenomedullin in anesthetized rat","volume":"219","author":"Watanabe","year":"1996","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"170347","DOI":"10.1016\/j.peptides.2020.170347","article-title":"Adrenomedullin\u2013Current perspective on a peptide hormone with significant therapeutic potential","volume":"131","author":"Fischer","year":"2020","journal-title":"Peptides"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/30666","article-title":"RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor","volume":"393","author":"McLatchie","year":"1998","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0014-5793(99)00358-0","article-title":"The RAMP2\/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells","volume":"448","author":"Kamitani","year":"1999","journal-title":"FEBS Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/bs.apha.2020.01.001","article-title":"RAMPs as allosteric modulators of the calcitonin and calcitonin-like class B G protein-coupled receptors","volume":"88","author":"Pioszak","year":"2020","journal-title":"Adv. Pharmacol."},{"key":"ref_14","first-page":"203","article-title":"SPECT and PET imaging of adrenomedullin receptors: A promising strategy for studying pulmonary vascular diseases","volume":"9","author":"Harel","year":"2019","journal-title":"Am. J. Nucl. Med. Mol. Imaging"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1042\/CS20040357","article-title":"Biodistribution, plasma kinetics and quantification of single-pass pulmonary clearance of adrenomedullin","volume":"109","author":"Dupuis","year":"2005","journal-title":"Clin. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1161\/CIRCRESAHA.123.321673","article-title":"Clinical Potential of Adrenomedullin Signaling in the Cardiovascular System","volume":"132","author":"Tian","year":"2023","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/s41440-021-00806-y","article-title":"Translational studies of adrenomedullin and related peptides regarding cardiovascular diseases","volume":"45","author":"Kita","year":"2022","journal-title":"Hypertens. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s00535-020-01741-4","article-title":"Adrenomedullin for steroid-resistant ulcerative colitis: A randomized, double-blind, placebo-controlled phase-2a clinical trial","volume":"56","author":"Kita","year":"2021","journal-title":"J. Gastroenterol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1111\/jgh.15945","article-title":"Adrenomedullin for biologic-resistant Crohn\u2019s disease: A randomized, double-blind, placebo-controlled phase 2a clinical trial","volume":"37","author":"Kita","year":"2022","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ashizuka, S., Kita, T., Inatsu, H., and Kitamura, K. (2021). Adrenomedullin: A Novel Therapeutic for the Treatment of Inflammatory Bowel Disease. Biomedicines, 9.","DOI":"10.3390\/biomedicines9081068"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1096\/fj.10-170316","article-title":"Anti-inflammatory actions of adrenomedullin through fine tuning of HIF stabilization","volume":"25","author":"MacManus","year":"2011","journal-title":"FASEB J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1007\/s00384-011-1254-0","article-title":"Impact of adrenomedullin on dextran sulfate sodium-induced inflammatory colitis in mice: Insights from in vitro and in vivo experimental studies","volume":"26","author":"Hayashi","year":"2011","journal-title":"Int. J. Color. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1002\/2211-5463.13577","article-title":"Adrenomedullin alleviates mucosal injury in experimental colitis and increases claudin-4 expression in the colonic epithelium","volume":"13","author":"Kawaguchi","year":"2023","journal-title":"FEBS Open Bio"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3615","DOI":"10.3892\/mmr.2015.3887","article-title":"Adrenomedullin improves intestinal epithelial barrier function by downregulating myosin light chain phosphorylation in ulcerative colitis rats","volume":"12","author":"Yi","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Geven, C., Kox, M., and Pickkers, P. (2018). Adrenomedullin and Adrenomedullin-Targeted Therapy As Treatment Strategies Relevant for Sepsis. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00292"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1097\/FJC.0b013e3181f15b45","article-title":"The first clinical pilot study of intravenous adrenomedullin administration in patients with acute myocardial infarction","volume":"56","author":"Kataoka","year":"2010","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/DDDT.S225220","article-title":"Safety, Tolerability, and Pharmacokinetics of Adrenomedullin in Healthy Males: A Randomized, Double-Blind, Phase 1 Clinical Trial","volume":"14","author":"Kita","year":"2020","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1248\/bpb.b20-00373","article-title":"Activation of Calcitonin Gene-Related Peptide and Adrenomedullin Receptors by PEGylated Adrenomedullin","volume":"43","author":"Akashi","year":"2020","journal-title":"Biol. Pharm. Bull."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"366","DOI":"10.3390\/gidisord2040033","article-title":"20 kDa PEGylated Adrenomedullin as a New Therapeutic Candidate for Inflammatory Bowel Disease","volume":"2","author":"Miki","year":"2020","journal-title":"Gastrointest. Disord."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/ddr.21383","article-title":"Anti-Inflammatory Effects of PEGylated Human Adrenomedullin in a Mouse DSS-Induced Colitis Model","volume":"78","author":"Nagata","year":"2017","journal-title":"Drug Dev. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e10600","DOI":"10.1002\/btm2.10600","article-title":"PEGylated therapeutics in the clinic","volume":"9","author":"Gao","year":"2024","journal-title":"Bioeng. Transl. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"26746","DOI":"10.1038\/s41598-025-10613-x","article-title":"Comparison between long-acting pegylated and daily recombinant human growth hormone for pediatric growth hormone deficiency a systematic review","volume":"15","author":"Zhang","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"29602","DOI":"10.1074\/jbc.M004534200","article-title":"Visualization of the calcitonin receptor-like receptor and its receptor activity-modifying proteins during internalization and recycling","volume":"275","author":"Kuwasako","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Hung, K.Y., Kowalczyk, R., Desai, A., Brimble, M.A., Marshall, J.F., and Harris, P.W.R. (2022). Synthesis and Systematic Study on the Effect of Different PEG Units on Stability of PEGylated, Integrin-\u03b1v\u03b26-Specific A20FMDV2 Analogues in Rat Serum and Human Plasma. Molecules, 27.","DOI":"10.3390\/molecules27144331"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1161\/hc4001.097191","article-title":"Vasopeptidase inhibitors: A new therapeutic concept in cardiovascular disease?","volume":"104","author":"Corti","year":"2001","journal-title":"Circulation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.bbrc.2020.06.057","article-title":"Thrombin rapidly digests adrenomedullin: Synthesis of adrenomedullin analogs resistant to thrombin","volume":"529","author":"Nishimoto","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5695","DOI":"10.1021\/acs.jmedchem.6b00126","article-title":"Adrenomedullin 2.0: Adjusting Key Levers for Metabolic Stability","volume":"59","author":"Schonauer","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/jemt.10047","article-title":"Identification, characterization, and physiological actions of factor H as an adrenomedullin binding protein present in human plasma","volume":"57","author":"Elsasser","year":"2002","journal-title":"Microsc. Res. Tech."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"12292","DOI":"10.1074\/jbc.M007822200","article-title":"Complement factor H is a serum-binding protein for adrenomedullin, and the resulting complex modulates the bioactivities of both partners","volume":"276","author":"Pio","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nrd1033","article-title":"Effect of pegylation on pharmaceuticals","volume":"2","author":"Harris","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1093\/jb\/mvab057","article-title":"Development of a novel human adrenomedullin derivative: Human serum albumin-conjugated adrenomedullin","volume":"170","author":"Kuroishi","year":"2021","journal-title":"J. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Nagata, S., Yamasaki, M., Kuroishi, N., and Kitamura, K. (2022). Development of Long-Acting Human Adrenomedullin Fc-Fusion Proteins. Biology, 11.","DOI":"10.3390\/biology11071074"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"14022","DOI":"10.1021\/acsnano.1c05922","article-title":"Polyethylene Glycol Immunogenicity: Theoretical, Clinical, and Practical Aspects of Anti-Polyethylene Glycol Antibodies","volume":"15","author":"Chen","year":"2021","journal-title":"ACS Nano"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Li, C., Li, T., Tian, X., An, W., Wang, Z., Han, B., Tao, H., Wang, J., and Wang, X. (2024). Research progress on the PEGylation of therapeutic proteins and peptides (TPPs). Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1353626"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1023\/A:1015396825274","article-title":"Pharmaceutical strategies utilizing recombinant human serum albumin","volume":"19","author":"Chuang","year":"2002","journal-title":"Pharm. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"103291","DOI":"10.1016\/j.jaut.2024.103291","article-title":"Telitacicept: A novel horizon in targeting autoimmunity and rheumatic diseases","volume":"148","author":"Zeng","year":"2024","journal-title":"J. Autoimmun."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Hosoda, H., Nakamura, T., and Yoshihara, F. (2022). Plasma Clearance of Intravenously Infused Adrenomedullin in Rats with Acute Renal Failure. Biomolecules, 12.","DOI":"10.3390\/biom12091281"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"171118","DOI":"10.1016\/j.peptides.2023.171118","article-title":"Receptor activity-modifying proteins of adrenomedullin (RAMP2\/3): Roles in the pathogenesis of ARDS","volume":"171","author":"Kasahara","year":"2024","journal-title":"Peptides"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines: Minimum information for publication of quantitative real-time PCR experiments","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1089\/neu.2009.1094","article-title":"Adrenomedullin prevents sex-dependent impairment of autoregulation during hypotension after piglet brain injury through inhibition of ERK MAPK upregulation","volume":"27","author":"Armstead","year":"2010","journal-title":"J. Neurotrauma"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1161\/CIRCRESAHA.118.313835","article-title":"Adrenomedullin Induces Cardiac Lymphangiogenesis After Myocardial Infarction and Regulates Cardiac Edema Via Connexin 43","volume":"124","author":"Trincot","year":"2019","journal-title":"Circ. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4515","DOI":"10.2147\/JIR.S366290","article-title":"Fibromodulin Ablation Exacerbates the Severity of Acute Colitis","volume":"15","author":"Halasi","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1002\/ibd.21557","article-title":"Pharmacological intervention studies using mouse models of the inflammatory bowel diseases: Translating preclinical data into new drug therapies","volume":"17","author":"Koboziev","year":"2011","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S0169-409X(02)00022-4","article-title":"Chemistry for peptide and protein PEGylation","volume":"54","author":"Roberts","year":"2002","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1046\/j.1365-2249.1999.00985.x","article-title":"Inhibition of dextran sulphate sodium (DSS)-induced colitis in mice by intracolonically administered antibodies against adhesion molecules (endothelial leucocyte adhesion molecule-1 (ELAM-1) or intercellular adhesion molecule-1 (ICAM-1))","volume":"117","author":"Hamamoto","year":"1999","journal-title":"Clin. Exp. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/19\/9373\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:49:37Z","timestamp":1760035777000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/19\/9373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,25]]},"references-count":56,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms26199373"],"URL":"https:\/\/doi.org\/10.3390\/ijms26199373","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,25]]}}}