Caveolin-1, Id3a and two LIM protein genes are upregulated by estrogen in vascular smooth muscle cells.
Estrogen has diverse effects on the vasculature, such as vasodilation, endothelial growth and inhibition of vascular smooth muscle cell (VSMC) proliferation and migration. However, little is known about the genes that are regulated by estrogen in the vascular wall. Wistar rats were ovariectomized or sham-operated (Sham group), and 2 weeks after the operation, were subjected to subcutaneous implantation of placebo pellets (OVX + V group) or estradiol pellets (OVX + E group). Endothelium-denuded aortic tissue was examined 2 weeks after implantation. By applying high-density oligonucleotide microarray analysis, the expression of approximately 7000 genes was analyzed. Among the genes with different expression levels between the OVX + E group and the OVX + V group, those that have been reported to be expressed in the vasculature or muscle tissue, were chosen. Finally, four genes, caveolin-1, two LIM proteins (enigma and SmLIM) and Id3a, were identified. Microarray as well as real-time polymerase chain reaction showed that the expression levels of these genes were significantly higher in the OVX + E group than in the OVX + V group. To clarify whether estrogen directly upregulates these genes in the vascular wall, Northern blot analysis was performed using cultured rat VSMC. Addition of 100 nmol/L estradiol for 24 hours increased the mRNA levels of all four genes. Although the precise mechanism remains unclear, regulation of these genes by estrogen might contribute to its effect on VSMC.
Watanabe
Tokumitsu
T
Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
Akishita
Masahiro
M
Nakaoka
Takashi
T
He
Hong
H
Miyahara
Yukiko
Y
Yamashita
Naohide
N
Wada
Youichiro
Y
Aburatani
Hiroyuki
H
Yoshizumi
Masao
M
Kozaki
Koichi
K
Ouchi
Yasuyoshi
Y
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001013:Aorta, Thoracic; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D051242:Caveolin 1; D022461:Caveolins / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D051796:Inhibitor of Differentiation Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010052:Ovariectomy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C495537:Cav1 protein, rat; D051242:Caveolin 1; D022461:Caveolins; C484375:Csrp2 protein, rat; D003598:Cytoskeletal Proteins; D051796:Inhibitor of Differentiation Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C484380:PDLIM7 protein, human; C099008:Pdlim7 protein, rat; D012333:RNA, Messenger; C075640:ID3 protein, human; D004958:Estradiol