{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:51:37Z","timestamp":1784735497508,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Midkine (MDK) is a multifunctional heparin-binding growth factor, and has been shown to regulate cell growth, survival, and migration. It also plays important roles in several inflammatory diseases such as sepsis. However, the role of MDK in the lungs has not yet been elucidated. In the present study, we investigated the role of MDK in pulmonary inflammation experiments using a mouse lipopolysaccharide (LPS)-induced pulmonary inflammation model and human bronchial cells. Wild-type and MDK-deficient mice were administered intratracheally with LPS, and several inflammatory parameters were analyzed. In the wild-type mice, MDK mRNA and protein in lung tissues were significantly increased after intratracheal LPS administration. The MDK-deficient mice showed significantly lower counts of total cells and neutrophils, as well as lower concentrations of total protein and neutrophil chemokines, KC and MIP-2 in bronchoalveolar lavage fluid, compared to wild-type mice. Moreover, mRNA expressions of TNF-\u03b1, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-2 in lung tissues, as well as the histopathological lung inflammation score, were significantly lower in the MDK-deficient mice. Furthermore, in in vitro experiments using bronchial epithelial cells, LPS stimulation increased mRNA expression of MDK, and MDK knockdown by siRNA decreased LPS-induced TNF-\u03b1 and CXCL8 upregulation. These findings suggest that deficiency of MDK attenuates LPS-induced pulmonary inflammation, at least in part, through inhibiting inflammatory cytokine and chemokine upregulation in the lungs.<\/jats:p>","DOI":"10.3390\/ijms26178519","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T15:02:57Z","timestamp":1756825377000},"page":"8519","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Midkine Deficiency Attenuates Lipopolysaccharide-Induced Pulmonary Inflammation"],"prefix":"10.3390","volume":"26","author":[{"given":"Yoshinori","family":"Tanino","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, Fukushima City 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xintao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, Fukushima City 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takefumi","family":"Nikaido","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, Fukushima City 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, Fukushima City 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuichi","family":"Togawa","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, Fukushima City 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsumi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, Fukushima City 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3370-0452","authenticated-orcid":false,"given":"Mishie","family":"Tanino","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology, Asahikawa Medical University Hospital, Asahikawa 078-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Kadomatsu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Nagoya University School of Medicine, Nagoya 464-8601, Japan"},{"name":"Institute for Glyco-Core Research, Nagoya University, Nagoya 464-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1794-0026","authenticated-orcid":false,"given":"Yoko","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, Fukushima City 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1056\/NEJMra1608077","article-title":"Acute respiratory distress syndrome","volume":"377","author":"Thompson","year":"2017","journal-title":"N. 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