Differences in E2F subunit expression in quiescent and proliferating vascular smooth muscle cells.
E2F is a family of transcriptional factors that control G(1)/S transition. We investigated how the E2F family participates in the biological responses of vascular smooth muscle cells (VSMC) to vasoconstrictive hormones compared with fetal bovine serum (FBS). FBS induced upregulation of E2F-1 and E2F-5 at both mRNA and protein levels and slightly reduced E2F-3 protein. Angiotensin II (ANG II) and arginine vasopressin increased E2F-3 protein, but not E2F-1 and E2F-5, without upregulating its mRNA level. FBS transactivated the E2F-1 gene through the induction of free E2F-1 binding onto its promoter, whereas ANG II-induced binding of E2F-3 did not result in activation of the E2F-1 promoter. These changes are responsible for hypertrophic or hyperplastic response of VSMC to different growth factors or stimulants. In contrast, both FBS and vasoconstrictive hormones drove transcription of the cdc6 gene by downregulating p130 and recruiting free E2F-3 in the latter, which underlies the progression of VSMC into S phase.
Fujita
Nobuya
N
Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical School, Tochigi, Japan.
Furukawa
Yusuke
Y
Itabashi
Naoki
N
Okada
Koji
K
Saito
Toshikazu
T
Ishibashi
Shun
S
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050703:E2F2 Transcription Factor; D050699:E2F3 Transcription Factor; D050704:E2F4 Transcription Factor; D050700:E2F5 Transcription Factor; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D021122:Protein Subunits; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050703:E2F2 Transcription Factor; D050699:E2F3 Transcription Factor; D050704:E2F4 Transcription Factor; D050700:E2F5 Transcription Factor; C493755:E2f1 protein, rat; C490489:E2f5 protein, rat; D021122:Protein Subunits; D012333:RNA, Messenger; D014157:Transcription Factors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D001127:Arginine Vasopressin