{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:50:20Z","timestamp":1788544220130,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"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>Cell signaling mediated by the \u03b1v integrin plays a pivotal role in macrophage activation in various inflammatory processes, but its involvement in the pathogenesis of dry eye disease (DED) remains unclear. In a murine model of DED, we found increased \u03b1v integrin expression in ocular surface macrophages. The \u03b1v integrins inhibitor c(RGDfK) ameliorated the corneal damage caused by DED, suggesting a pathogenic role for \u03b1v integrin. Because tear hyperosmolarity induces ocular inflammation in DED, a hyperosmolar culture of murine bone marrow-derived macrophages (BMDMs) is used to reproduce inflammation in vitro. However, the expression of proinflammatory cytokine mRNA was minimal, even though \u03b1v integrin was induced. In searching for components that are involved in \u03b1v integrin-mediated inflammation but that are missing from the culture model, we showed that the levels of vitronectin (VTN), a binding ligand of \u03b1v integrins, were increased in the tear fluid and conjunctival stroma of DED animals. The addition of VTN prominently enhanced hyperosmolarity-induced inflammation in BMDMs. Mechanistically, we showed that VTN\/\u03b1v integrins mediated NF-\u03baB activation to induce inflammatory gene expression in the BMDMs. Our findings indicate that interaction the of VTN with \u03b1v integrins is a crucial step in the inflammatory process in DED and suggests a novel therapeutic target.<\/jats:p>","DOI":"10.3390\/ijms22168410","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T09:35:32Z","timestamp":1628156132000},"page":"8410","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Integrin \u03b1v and Vitronectin Prime Macrophage-Related Inflammation and Contribute the Development of Dry Eye Disease"],"prefix":"10.3390","volume":"22","author":[{"given":"Tsung-Chuan","family":"Ho","sequence":"first","affiliation":[{"name":"Department of Medical Research, Mackay Memorial Hospital, New Taipei City 25160, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-I","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mackay Medical College, New Taipei City 25245, Taiwan"},{"name":"Department of Ophthalmology, Mackay Memorial Hospital, Taipei 10449, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Show-Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Department and Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeou-Ping","family":"Tsao","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Mackay Memorial Hospital, New Taipei City 25160, Taiwan"},{"name":"Department of Medicine, Mackay Medical College, New Taipei City 25245, Taiwan"},{"name":"Department of Ophthalmology, Mackay Memorial Hospital, Taipei 10449, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S1542-0124(12)70081-2","article-title":"The definition and classification of dry eye disease: Report of the Definition and Classification Subcommittee of the International Dry Eye Workshop","volume":"5","author":"Listed","year":"2007","journal-title":"Ocul. 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