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Protein expression was comprehensively quantified at the BBB of experimental autoimmune encephalomyelitis (EAE) mice, a model of multiple sclerosis, using the SWATH method. Concerning tight junction molecules, the level of expression of Claudin\u20105, which, in a previous immunohistochemical analysis, was confirmed to be down\u2010regulated by EAE, remained unchanged, but the expression of Claudin\u201011 and Occludin was decreased by 0.69\u2010 and 0.62\u2010fold, respectively, in brain capillaries isolated from EAE mice. A number of other cell\u2013cell junctional molecules including ESAM, CADM1, CADM2, CADM3, CADM4, and HEPACAM were also down\u2010regulated. The levels of expression of intercellular adhesion molecule 1 (ICAM1) and vascular cell adhesion molecule 1 (VCAM1), which directly mediate the infiltration of lymphocytes across the BBB, were increased in EAE mice by 3.3\u2010 and 2.6\u2010fold, respectively. The expression of CXADR, which possibly facilitates the adhesion of migrating cells, was also increased by 3.5\u2010fold. Interestingly, various members of the Annexin A (ANXA) family were also up\u2010regulated in brain capillaries that were isolated from EAE mice. In a pathway associated with cell infiltration and tight junction disruption, a series of molecules that are involved in ANXA2 signaling (ANXA2, PTP1B, Ahnak, S100A11, CD44, Kindlin2, Integrin \u03b15, Fibronectin, Fibrinogen) were up\u2010regulated. ANXA2 is selectively and abundantly expressed in endothelial cells in the brain. The daily administration of an ANXA2 inhibitor (LCKLSL peptide) significantly suppressed the development of EAE in mice. In summary, the activation of ANXA2 signaling at the BBB appear to play an important role in the pathogenesis of EAE.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15578-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15578","type":"journal-article","created":{"date-parts":[[2022,1,22]],"date-time":"2022-01-22T16:27:51Z","timestamp":1642868871000},"page":"662-674","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Activation of Annexin <scp>A2<\/scp> signaling at the blood\u2013brain barrier in a mouse model of multiple sclerosis"],"prefix":"10.1111","volume":"160","author":[{"given":"Kenta","family":"Tezuka","sequence":"first","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayoshi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risa","family":"Sato","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Kawarada","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6332-7575","authenticated-orcid":false,"given":"Tetsuya","family":"Terasaki","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9860-1979","authenticated-orcid":false,"given":"Yasuo","family":"Uchida","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808698106"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199655100-00006"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.313545"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.07.004"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.O111.016717"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(00)00036-X"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-017-0158-2"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-008-9532-4"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90367-Y"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5461"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.469408"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.04.051"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa418"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-018-0145-7"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21845"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi061754e"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0710432"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b18-00939"},{"key":"e_1_2_10_20_1","first-page":"189","article-title":"Evidence for involvement of ICAM\u20101 and VCAM\u20101 in lymphocyte interaction with endothelium in experimental autoimmune encephalomyelitis in the central nervous system in the SJL\/J mouse","volume":"145","author":"Steffen B. 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