Involvement of NF-kappa B activation in thrombin-induced human vascular smooth muscle cell proliferation.
A thrombin receptor has been cloned and is thought to mediate a variety of thrombin-induced responses. However, the transcription factors important for postreceptor signaling have been little clarified. The post-receptor signals are mediated by several protein kinases responsible for NF-kappa B activation, and most thrombin-inducible genes have the kappa B sequence in the regulatory elements. The possibility that NF-kappa B may participate in thrombin signaling was therefore investigated in cultured human vascular smooth muscle cells (VSMCs). Thrombin receptor stimulation resulted in activation of NF-kappa B. Furthermore, treatment of cells with antisense p65 ODNs of NF-kappa B inhibited thrombin-stimulated growth of VSMC in vitro. Results indicate that the activation of NF-kappa B is involved in thrombin signaling and that this pathway causes the proliferation of VSMC induced by thrombin. Therapeutic potential of antisense NF-kappa B ODNs for the treatment with atherosclerosis and restenosis is also indicated.
Department of Laboratory Medicine, Faculty of Medicine, University of Kagoshima, Japan.
T
T
Nakajima
I
I
Kitajima
H
H
Shin
I
I
Takasaki
K
K
Shigeta
K
K
Abeyama
Y
Y
Yamashita
T
T
Tokioka
Y
Y
Soejima
I
I
Maruyama
D000135:Acid Phosphatase / Q000494:pharmacology; D000595:Amino Acid Sequence; D001483:Base Sequence; D002455:Cell Division; D002478:Cells, Cultured; D006801:Humans; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*
D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D000135:Acid Phosphatase; D013917:Thrombin