PDGF-D induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis.
Platelet-derived growth factor-D (PDGF-D) is a recently characterized member of the PDGF family with unknown in vivo functions. We investigated the effects of PDGF-D in transgenic mice by expressing it in basal epidermal cells and then analyzed skin histology, interstitial fluid pressure, and wound healing. When compared with control mice, PDGF-D transgenic mice displayed increased numbers of macrophages and elevated interstitial fluid pressure in the dermis. Wound healing in the transgenic mice was characterized by increased cell density and enhanced recruitment of macrophages. Macrophage recruitment was also the characteristic response when PDGF-D was expressed in skeletal muscle or ear by an adeno-associated virus vector. Combined expression of PDGF-D with vascular endothelial growth factor-E (VEGF-E) led to increased pericyte/smooth muscle cell coating of the VEGF-E-induced vessels and inhibition of the vascular leakiness that accompanies VEGF-E-induced angiogenesis. These results show that full-length PDGF-D is activated in tissues and is capable of increasing interstitial fluid pressure and macrophage recruitment and the maturation of blood vessels in angiogenic processes.
Molecular/Cancer Biology Laboratory, Ludwig Institute for Cancer Research, Helsinki University, Finland.
Marko
M
Uutela
Maria
M
Wirzenius
Karri
K
Paavonen
Iiro
I
Rajantie
Yulong
Y
He
Terhi
T
Karpanen
Marja
M
Lohela
Helge
H
Wiig
Petri
P
Salven
Katri
K
Pajusola
Ulf
U
Eriksson
Kari
K
Alitalo
D000818:Animals; D001808:Blood Vessels / Q000502:physiology; D002465:Cell Movement / Q000276:immunology; D020405:Dermis / Q000502:physiology; D045604:Extracellular Fluid / Q000502:physiology; D006801:Humans; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000235:genetics* / Q000378:metabolism*; D011312:Pressure; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics; D014945:Wound Healing
D008222:Lymphokines; C427493:PDGFD protein, human; C498951:Pdgfd protein, mouse; D010982:Platelet-Derived Growth Factor; C084758:VEGF-like protein, Orf virus; D014764:Viral Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2