title: Placenta growth factor and vascular endothelial growth factor B and C expression in microvascular endothelial cells and pericytes. Implication in autocrine and paracrine regulation of angiogenesis.
abstract: We have shown previously that vascular endothelial growth factor (VEGF) synthesized by the cellular constituents of small vessels per se, viz. endothelial cells and pericytes, participates in the hypoxia-driven proliferation of both cell types (Nomura, M., Yamagishi, S., Harada, S., Hayashi, Y., Yamashima, T., Yamashita, J., Yamamoto, H. (1995) J. Biol. Chem. 270, 28316-28324; Yamagishi, S., Yonekura, H., Yamamoto, Y., Fujimori, H., Sakurai, S., Tanaka, N., and Yamamoto, H. (1999) Lab. Invest. 79, 501-509). In this study, we examined the expression of the recently isolated VEGF gene family members (placenta growth factor (PlGF), VEGF-B, and VEGF-C) in human dermal microvascular endothelial cells and bovine retinal pericytes cultured under various oxygen tensions. Quantitative reverse transcription-polymerase chain reaction analyses demonstrated that the two cell types possess not only VEGF (VEGF-A) mRNA, but also VEGF-B, VEGF-C, and PlGF mRNAs. Among them, only VEGF-A mRNA was induced under hypoxia. Competitive reverse transcription-polymerase chain reaction showed that, under normoxic conditions, the rank order of mRNA content in endothelial cells was PlGF > VEGF-B > VEGF-C > VEGF-A and that mRNA coding for PlGF was expressed at >100-fold higher levels than VEGF-A mRNA. In pericytes, the rank order was VEGF-C > VEGF-A > VEGF-B > PlGF, and approximately 7-fold higher levels of VEGF-C mRNA compared with VEGF-A mRNA were noted in this cell type. Furthermore, antisense inhibition of PlGF protein production lowered the endothelial cell synthesis of DNA under hypoxic conditions. The results suggest that these VEGF family members may also take active parts in angiogenesis.
authors.affiliation: Department of Biochemistry, Kanazawa University School of Medicine, Kanazawa 920-8640, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yonekura
authors.forename: S
authors.initials: S
authors.lastname: Sakurai
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Migita
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Yamagishi
authors.forename: M
authors.initials: M
authors.lastname: Nomura
authors.forename: M J
authors.initials: MJ
authors.lastname: Abedin
authors.forename: H
authors.initials: H
authors.lastname: Unoki
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D015687:Cell Hypoxia; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense; D020286:Pericytes / Q000378:metabolism*; D000072483:Placenta Growth Factor; D011233:Precipitin Tests; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D042582:Vascular Endothelial Growth Factor C
chemical_list: D016228:Endothelial Growth Factors; D016376:Oligonucleotides, Antisense; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D042582:Vascular Endothelial Growth Factor C; D000072483:Placenta Growth Factor