Stimulation of in vitro angiogenesis by nitric oxide through the induction of transcription factor ETS-1.
The aim of this study was to examine whether transcription factor ETS-1, which is responsible for the expression of metalloproteinases and integrin beta(3), is implicated in the induction of nitric oxide (NO)-induced angiogenesis. Bovine aortic endothelial cells were cultured on type I collagen gel to measure the length of the formed tube-like structure, which is a marker for in vitro angiogenesis. The addition of S-nitroso-N-acetylpenicillamine (SNAP), an NO-donor, to confluent endothelial cells stimulated the formation of the tube-like structure, with disappearance of covered endothelial cell monolayers. Another NO-donor 2,2'-(hydroxynitrosohydrazono)bis-ethanamine (NOC 18) also induced the formation of the tube-like structure. In contrast to the induction of the formation of the tube-like structure by SNAP, it reduced cell proliferation. SNAP and NOC 18 also increased the expression of the ets-1 mRNA level in a concentration-dependent manner. The maximum expression was observed at 2h after their addition. Moreover, the SNAP-induced in vitro angiogenesis, ets-1 mRNA expression and ETS-1 protein expression were strongly reduced by the treatment with ets-1 antisense oligonucleotide. These results strongly suggest that NO stimulates in vitro angiogenesis through the induction of ETS-1 expression. NO appears to stimulate endothelial cell differentiation to the angiogenic phenotype via the induction of ETS-1 transcription factor.
Department of Pathophysiology, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. shun.@pharm.showa-u.ac.jp
Shunichi
S
Shimizu
Michie
M
Kageyama
Masako
M
Yasuda
Daisuke
D
Sasaki
Shinji
S
Naito
Toshinori
T
Yamamoto
Yuji
Y
Kiuchi
D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
D024042:Collagen Type I; C093285:NOC 18; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D016376:Oligonucleotides, Antisense; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; C110881:S-nitro-N-acetylpenicillamine; D014157:Transcription Factors; D009569:Nitric Oxide; D010396:Penicillamine