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微小血管細胞におけるVEGFファミリー遺伝子群の発現と機能 : 米倉秀人, 劉　暁旭, 右田秀幸, 野村素弘, 山岸昌一, 山本靖彦, 山本　博 (金沢大・医・生化二)

The expression and roles of the VEGF family in hypoxia-driven angiogenesis : Hideto YONEKURA, Xiaoxu LIU, Hideyuki MIGITA, Motohiro NOMURA, Sho-ichi YAMAGISHI, Yasuhiko YAMAMOTO and Hiroshi YAMAMOTO (Dept. of Biochem., Kanazawa Univ. Sch. of Med.)

We have shown previously that hypoxia induces the proliferation and tube formation of endothelial cells (EC) through an induction of autocrine VEGF¹. In the present study, we investigated the expression and roles of VEGF family genes (VEGF, VEGF-B, VEGF-C and PlGF) in the very cell types where angiogenesis takes place. Human skin microvascular EC and bovine retinal microvascular pericytes were cultured under various oxygen tensions, and assayed for the expression of the VEGF family genes. Both cell types possessed not only VEGF but also VEGF-B, -C and PlGF mRNAs. Competitive RT-PCR analyses ranked their levels in EC in the following order: PlGF > VEGF > VEGF-B, -C. EC expressed mRNAs for Kdr and Flt-1, the receptors for VEGF. In hypoxia-exposed EC, VEGF and PlGF mRNA levels increased, whereas those for VEGF-B and -C remained constant. Antisense DNA complements of PlGF as well as VEGF mRNA abolished hypoxia-driven EC synthesis of DNA. In pericytes, the levels of VEGF family mRNAs were ranked as VEGF-C > VEGF > VEGF-B > PlGF, and the predominant form of VEGF receptors was Flt-1. Pericytes grew in response to low oxygen, and this was fully neutralized by anti-VEGF antibodies, suggesting that VEGF can also act as a pericyte mitogen. The results thus indicate that the vascular members of the VEGF family may take an active part in the hypoxia-driven angiogenesis in autocrine and paracrine manners.
¹ J.Biol.Chem. 270, 28316 -28324 (1995)