| First Author | Nakamura K | Year | 2019 |
| Journal | J Cell Biol | Volume | 218 |
| Issue | 10 | Pages | 3506-3525 |
| PubMed ID | 31541017 | Mgi Jnum | J:280857 |
| Mgi Id | MGI:6364740 | Doi | 10.1083/jcb.201807178 |
| Citation | Nakamura K, et al. (2019) Perlecan regulates pericyte dynamics in the maintenance and repair of the blood-brain barrier. J Cell Biol 218(10):3506-3525 |
| abstractText | 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 PDGFRbeta 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 PDGFRbeta, SHP-2, and FAK partially through integrin alpha5beta1 and promoted pericyte migration. Perlecan therefore appears to regulate pericyte recruitment through the cooperative functioning of PDGFRbeta and integrin alpha5beta1 to support BBB maintenance and repair following ischemic stroke. |
