Mice overexpressing placenta growth factor exhibit increased vascularization and vessel permeability.
Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family, comprising at least five cytokines specifically involved in the regulation of vascular and/or lymphatic endothelium differentiation. Several lines of evidence indicate a role for PlGF in monocyte chemotaxis and in potentiating the activity of VEGF, but the exact function of this cytokine is not fully understood. To define the biological role of PlGF in vivo, we have produced a transgenic mouse model overexpressing this factor in the skin by using a keratin 14 promoter cassette. Our data indicate that PlGF has strong angiogenic properties in both fetal and adult life. PlGF overexpression results in a substantial increase in the number, branching and size of dermal blood vessels as well as in enhanced vascular permeability. Indeed, intradermally injected recombinant PlGF was able to induce vessel permeability in wild-type mice. The analysis of vascular endothelial growth factor receptor 1/flt-1 and vascular endothelial growth factor receptor 2/flk-1 indicates that the two receptors are induced in the skin endothelium of transgenic mice suggesting that both are involved in mediating the effect of overexpressed PlGF.
Odorisio
Teresa
T
Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell'Immacolata, IRCCS, 00167 Rome, Italy. t.odorisio@idi.it
Schietroma
Cataldo
C
Zaccaria
M Letizia
ML
Cianfarani
Francesca
F
Tiveron
Cecilia
C
Tatangelo
Laura
L
Failla
Cristina M
CM
Zambruno
Giovanna
G
D000818:Animals; D000831:Animals, Newborn; D002199:Capillary Permeability / Q000235:genetics*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D053547:Keratin-14; D007633:Keratins / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D018995:Myosin Heavy Chains; D018919:Neovascularization, Physiologic / Q000502:physiology*; D024501:Nonmuscle Myosin Type IIB; D000072483:Placenta Growth Factor; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012867:Skin / Q000098:blood supply* / Q000166:cytology / Q000254:growth & development*; D015854:Up-Regulation / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D053547:Keratin-14; C507446:Krt14 protein, mouse; C000608037:Pgf protein, mouse; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D000072483:Placenta Growth Factor; D007633:Keratins; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains