Perlecan regulates pericyte dynamics in the maintenance and repair of the blood–brain barrier

• DOI: 10.1083/jcb.201807178
• Publication Date: 2019-09-20T20:05:17Z
• Authors: Kuniyuki Nakamura; Tomoko Ikeuchi; Kazuki Nara; Craig S. Rhodes; Peipei Zhang; Yuta Chiba; Saiko Kazuno; Yoshiki Miura; Tetsuro Ago; Eri Arikawa-Hirasawa; Yoh-suke Mukouyama; Yoshihiko Yamada
• Keywords: Perlecan; Pericyte

Ischemic stroke causes blood–brain barrier (BBB) breakdown due to significant damage the integrity of BBB components. Recent studies have highlighted importance pericytes in repair process functions triggered by PDGFRβ up-regulation. Here, we show that perlecan, a major heparan sulfate proteoglycan basement membranes, aids maintenance and through pericyte interactions. Using transient middle cerebral artery occlusion model, found larger infarct volumes more leakage conditional perlecan (Hspg2)-deficient (Hspg2−/−-TG) mice than control mice. Control showed increased numbers ischemic lesion, whereas Hspg2−/−-TG did not. At mechanistic level, attached recombinant C-terminal domain V (perlecan DV, endorepellin). Perlecan DV enhanced PDGF-BB–induced phosphorylation PDGFRβ, SHP-2, FAK partially integrin α5β1 promoted migration. therefore appears regulate recruitment cooperative functioning support following stroke.