Mice Lacking Platelet-Derived Growth Factor D Display a Mild Vascular Phenotype

Abstract

Platelet-derived growth factor D (PDGF-D) is the most recently discovered member of the PDGF family. PDGF-D signals through PDGF receptor β, but its biological role remains largely unknown. 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. Here, we present the phenotype of a constitutive Pdgfd knockout mouse model (Pdgfd-/-), carrying a LacZ reporter used to visualize Pdgfd promoter activity. 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. We show that Pdgfd reporter gene activity was consistently localized to vascular structures in both postnatal and adult tissues. The expression was predominantly arterial, often localizing to vascular bifurcations. Endothelial cells appeared to be the dominating source for Pdgfd, but reporter gene activity was occasionally also found in subpopulations of mural cells. Tissue-specific analyses of vascular structures revealed that NG2-expressing pericytes of the cardiac vasculature were disorganized in Pdgfd-/- mice. Furthermore, Pdgfd-/- mice also had a slightly elevated blood pressure. 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.

Cytomegalovirus promotes murine glioblastoma growth via pericyte recruitment and angiogenesis

“…This identified 6 mRNAs with potential proangiogenic roles upregulated in HCMV-infected GSCs: BMP4 (33), CCL2 (34), CXCL8 (35), LIF (36), WNT4 (37), and PDGFD, as shown in Supplemental Table 1. Of these, PDGF-D, a known regulator of pericyte function (38)(39)(40), has not been studied in GBM. Because of the pronounced effect on pericytes in our mouse model, we further investigated the potential role of PDGF-D in mediating the observed phenotypes.…”

Involvement of platelet‐derived growth factor ligands and receptors in tumorigenesis

“…Moreover, the kidney function was perturbed after knockout of PDGFB or PDGFR β because of defect development of mesangial cells. Knockout of the gene for the other PDGFRβ ligand, PDGF‐DD, revealed a mild vascular phenotype with disorganized pericytes and elevated blood pressure . These observations suggest that PDGF‐BB is the more important ligand for PDGFRβ during embryonal development, but that PDGF‐DD has a function in the maintenance of vascular homeostasis.…”

Neuropilin 1 binds PDGF-D and is a co-receptor in PDGF-D–PDGFRβ signaling

“…It has a mainly arterial vascular expression pattern ( Gladh et al, 2016), suggesting that its interaction with NRP1 and activation of PDGFRβ might be involved in spatial regulatory mechanisms in mural cells or between endothelial cells and adjacent pericytes. Many fundamental vascular processes depend on proper endothelial-to-pericyte communication, such as basement membrane formation, vascular stabilization, maintenance and remodeling (Armulik et al, 2011;Geevarghese and Herman, 2014).…”