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

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

研究成果: ジャーナルへの寄稿学術誌査読


Ischemic stroke causes blood-brain barrier (BBB) breakdown due to significant damage to the integrity of BBB components. Recent studies have highlighted the importance of pericytes in the repair process of BBB functions triggered by PDGFRβ 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- / --TG) mice than in control mice. Control mice showed increased numbers of pericytes in the ischemic lesion, whereas Hspg2- / --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-induced phosphorylation of PDGFRβ, SHP-2, and FAK partially through integrin α5β1 and promoted pericyte migration. Perlecan therefore appears to regulate pericyte recruitment through the cooperative functioning of PDGFRβ and integrin α5β1 to support BBB maintenance and repair following ischemic stroke.

ジャーナルThe Journal of cell biology
出版ステータス出版済み - 10月 7 2019


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