Transcriptional suppression of rat angiotensin AT1a receptor gene expression by interferon-γ in vascular smooth muscle cells

Yukio Ikeda, Kazuhisa Takeuchi, Taro Kato, Yoshihiro Taniyama, Kazunori Sato, Nobuyuki Takahashi, Akira Sugawara, Sadayoshi Ito

研究成果: Article査読

23 被引用数 (Scopus)

抄録

Angiotensin (Ang) II stimulates proliferation of vascular smooth muscle cells (VSMC) via its specific receptor AT1 subtype, possibly leading to atherosclerosis in hypertension. On the other hand, a cytokine interferon (IFN)-γ has been shown to have an anti-atherosclerotic effect. In the present study, we examined a possible role of IFN-γ in AT1 receptor gene regulation in VSMC. A firefly luciferase expression vector driven by the rat AT1a receptor gene promoter (~3.2 kb) was transfected into the cultured rat VSMC, and luciferase expression was determined to estimate the transcription function of the AT1a receptor gene promoter. RT-PCR was also carried out to determine mRNA expression of AT1a receptor in VSMC. IFN-γ treatment decreased AT1a receptor mRNA expression as well as luciferase expression in a dose-dependent manner. The analysis with deletion DNA fragments showed that the IFN-responsive element was located between -987 and -331 positions, where multiple GAS (gamma interferon activated site)-like elements were identified. The expression suppression was reversed by either a MAPKK inhibitor PD98059 or a Jak-2 inhibitor AG-490. These results suggest that IFN-γ can inhibit AT1 receptor expression at gene transcription level, and that the transcription suppression is dependent on MAP kinase and Jak-2. Inhibition of AT1a receptor expression may possibly be implicated in the anti-atherosclerotic action of IFN-γ in VSMC.

本文言語English
ページ(範囲)494-498
ページ数5
ジャーナルBiochemical and biophysical research communications
262
2
DOI
出版ステータスPublished - 1999 8 27

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

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