Deletion of the genes encoding the different PDGF ligands and receptors have shown that they are essential during embryonic development. PDGF-D is the only ligand that binds specifically to, and induces downstream signaling via PDGFRβ.
ANNA TANNENBERG ACTIVATOR
Serine proteases such as urokinase-type plasminogen activator (uPA) and matriptase can activate PDGF-D. PDGF-C and PDGF-D also contain an additional N-terminal CUB domain that requires proteolytic removal to enable receptor binding, and are thus secreted as latent dimers. PDGF-D shares the conserved growth factor domain with the other members of the family. The biological function of the PDGF family and their receptors has been extensively investigated, with the exception of PDGF-D.
They are all secreted as disulfide-bonded homo- or heterodimers, PDGF-AA, -AB, -BB, -CC and–DD, and exert their biological functions by binding to and signaling via two tyrosine kinase receptors, PDGF receptor (PDGFR)α and PDGFRβ. The platelet-derived growth factor (PDGF) family consists of four ligands, PDGF-A to -D. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the paper and its Supporting Information filesįunding: Funding for this work came from The Swedish Heart and Lung Foundation 2012-0077 ( The Swedish Cancer Foundation 2014/630 ( and The Swedish Research Council 2011-3861 ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. Received: NovemAccepted: MaPublished: March 31, 2016Ĭopyright: © 2016 Gladh et al. PLoS ONE 11(3):Įditor: Nikolaos Frangogiannis, Albert Einstein College of Medicine, UNITED STATES (2016) Mice Lacking Platelet-Derived Growth Factor D Display a Mild Vascular Phenotype. In summary, the vascular expression pattern together with morphological changes in NG2-expressing cells, and the increase in blood pressure, support a function for PDGF-D in regulating systemic arterial blood pressure, and suggests a role in maintaining vascular homeostasis.Ĭitation: Gladh H, Folestad EB, Muhl L, Ehnman M, Tannenberg P, Lawrence A-L, et al. Furthermore, Pdgfd -/- mice also had a slightly elevated blood pressure. Tissue-specific analyses of vascular structures revealed that NG2-expressing pericytes of the cardiac vasculature were disorganized in Pdgfd -/- mice. Endothelial cells appeared to be the dominating source for Pdgfd, but reporter gene activity was occasionally also found in subpopulations of mural cells. The expression was predominantly arterial, often localizing to vascular bifurcations. We show that Pdgfd reporter gene activity was consistently localized to vascular structures in both postnatal and adult tissues. Inactivation of the Pdgfd gene resulted in a mild phenotype in C57BL/6 mice, and the offspring was viable, fertile and generally in good health. Here, we present the phenotype of a constitutive Pdgfd knockout mouse model ( Pdgfd -/-), carrying a LacZ reporter used to visualize Pdgfd promoter activity. In contrast to other members of the PDGF family of growth factors, which have been extensively investigated using different knockout approaches in mice, PDGF-D has until now not been characterized by gene inactivation in mice. PDGF-D signals through PDGF receptor β, but its biological role remains largely unknown. Platelet-derived growth factor D (PDGF-D) is the most recently discovered member of the PDGF family.
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