| First Author | Naylor AJ | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 9 | Pages | e107146 |
| PubMed ID | 25243742 | Mgi Jnum | J:222506 |
| Mgi Id | MGI:5644763 | Doi | 10.1371/journal.pone.0107146 |
| Citation | Naylor AJ, et al. (2014) A differential role for CD248 (Endosialin) in PDGF-mediated skeletal muscle angiogenesis. PLoS One 9(9):e107146 |
| abstractText | CD248 (Endosialin) is a type 1 membrane protein involved in developmental and pathological angiogenesis through its expression on pericytes and regulation of PDGFRbeta signalling. Here we explore the function of CD248 in skeletal muscle angiogenesis. Two distinct forms of capillary growth (splitting and sprouting) can be induced separately by increasing microcirculatory shear stress (chronic vasodilator treatment) or by inducing functional overload (extirpation of a synergistic muscle). We show that CD248 is present on pericytes in muscle and that CD248-/- mice have a specific defect in capillary sprouting. In contrast, splitting angiogenesis is independent of CD248 expression. Endothelial cells respond to pro-sprouting angiogenic stimulus by up-regulating gene expression for HIF1alpha, angiopoietin 2 and its receptor TEK, PDGF-B and its receptor PDGFRbeta; this response did not occur following a pro-splitting angiogenic stimulus. In wildtype mice, defective sprouting angiogenesis could be mimicked by blocking PDGFRbeta signalling using the tyrosine kinase inhibitor Imatinib mesylate. We conclude that CD248 is required for PDGFRbeta-dependant capillary sprouting but not splitting angiogenesis, and identify a new role for CD248 expressed on pericytes in the early stages of physiological angiogenesis during muscle remodelling. |
