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Recent studies have highlighted the importance of pericytes in the repair process of BBB functions triggered by PDGFR\u03b2 up-regulation. Here, we show that perlecan, a major heparan sulfate proteoglycan of basement membranes, aids in BBB maintenance and repair through pericyte interactions. Using a transient middle cerebral artery occlusion model, we found larger infarct volumes and more BBB leakage in conditional perlecan (Hspg2)-deficient (Hspg2\u2212\/\u2212-TG) mice than in control mice. Control mice showed increased numbers of pericytes in the ischemic lesion, whereas Hspg2\u2212\/\u2212-TG mice did not. At the mechanistic level, pericytes attached to recombinant perlecan C-terminal domain V (perlecan DV, endorepellin). Perlecan DV enhanced the PDGF-BB\u2013induced phosphorylation of PDGFR\u03b2, SHP-2, and FAK partially through integrin \u03b15\u03b21 and promoted pericyte migration. Perlecan therefore appears to regulate pericyte recruitment through the cooperative functioning of PDGFR\u03b2 and integrin \u03b15\u03b21 to support BBB maintenance and repair following ischemic stroke.<\/jats:p>","DOI":"10.1083\/jcb.201807178","type":"journal-article","created":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T16:05:17Z","timestamp":1568995517000},"page":"3506-3525","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":89,"title":["Perlecan regulates pericyte dynamics in the maintenance and repair of the blood\u2013brain barrier"],"prefix":"10.1083","volume":"218","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9918-8802","authenticated-orcid":true,"given":"Kuniyuki","family":"Nakamura","sequence":"first","affiliation":[{"name":"Molecular Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 1"},{"name":"Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Ikeuchi","sequence":"additional","affiliation":[{"name":"Molecular Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Nara","sequence":"additional","affiliation":[{"name":"Molecular Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 1"},{"name":"Tohoku University School of Medicine, Sendai, Japan 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig S.","family":"Rhodes","sequence":"additional","affiliation":[{"name":"Molecular Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peipei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Molecular Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Chiba","sequence":"additional","affiliation":[{"name":"Molecular Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5532-2547","authenticated-orcid":true,"given":"Saiko","family":"Kazuno","sequence":"additional","affiliation":[{"name":"Laboratory of Proteomics and Biomolecular Science, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo, Japan 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7596-0482","authenticated-orcid":true,"given":"Yoshiki","family":"Miura","sequence":"additional","affiliation":[{"name":"Laboratory of Proteomics and Biomolecular Science, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo, Japan 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuro","family":"Ago","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4959-4113","authenticated-orcid":true,"given":"Eri","family":"Arikawa-Hirasawa","sequence":"additional","affiliation":[{"name":"Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoh-suke","family":"Mukouyama","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cell and Neuro-Vascular Biology, Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Yamada","sequence":"additional","affiliation":[{"name":"Molecular Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2019,9,20]]},"reference":[{"key":"2023072315073256000_bib1","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1038\/15537","article-title":"Perlecan is essential for cartilage and cephalic development","volume":"23","author":"Arikawa-Hirasawa","year":"1999","journal-title":"Nat. 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