| First Author | Dubrac A | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 3463 |
| PubMed ID | 30150707 | Mgi Jnum | J:266482 |
| Mgi Id | MGI:6209254 | Doi | 10.1038/s41467-018-05926-7 |
| Citation | Dubrac A, et al. (2018) NCK-dependent pericyte migration promotes pathological neovascularization in ischemic retinopathy. Nat Commun 9(1):3463 |
| abstractText | Pericytes are mural cells that surround capillaries and control angiogenesis and capillary barrier function. During sprouting angiogenesis, endothelial cell-derived platelet-derived growth factor-B (PDGF-B) regulates pericyte proliferation and migration via the platelet-derived growth factor receptor-beta (PDGFRbeta). PDGF-B overexpression has been associated with proliferative retinopathy, but the underlying mechanisms remain poorly understood. Here we show that abnormal, alpha-SMA-expressing pericytes cover angiogenic sprouts and pathological neovascular tufts (NVTs) in a mouse model of oxygen-induced retinopathy. Genetic lineage tracing demonstrates that pericytes acquire alpha-SMA expression during NVT formation. Pericyte depletion through inducible endothelial-specific knockout of Pdgf-b decreases NVT formation and impairs revascularization. Inactivation of the NCK1 and NCK2 adaptor proteins inhibits pericyte migration by preventing PDGF-B-induced phosphorylation of PDGFRbeta at Y1009 and PAK activation. Loss of Nck1 and Nck2 in mural cells prevents NVT formation and vascular leakage and promotes revascularization, suggesting PDGFRbeta-Y1009/NCK signaling as a potential target for the treatment of retinopathies. |
