15-deoxy-Δ12,14-prostaglandin J2 induces G1 arrest and differentiation marker expression in vascular smooth muscle cells

Yoshikazu Miwa, Toshiyuki Sasaguri, Hiroyasu Inoue, Yoji Taba, Akio Ishida, Takeo Abumiya

研究成果: Contribution to journalArticle査読

41 被引用数 (Scopus)

抄録

In search of substances useful for the treatment of atherosclerotic vascular diseases, we studied the effects of 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a natural ligand for peroxisome proliferator-activated receptor γ, on the proliferation and differentiation of vascular smooth muscle cells (VSMCs). 15d-PGJ2 but not WY14643, an agonist for peroxisome proliferator-activated receptor α, dose-dependently inhibited VSMC proliferation; the effect was maximal at 12 μM. This compound strongly suppressed the activities of cyclin-dependent kinases (Cdk) 4, 6, and 2, thereby preventing the phosphorylation of the retinoblastoma protein. These Cdks seemed to be inhibited through two mechanisms: the down-regulation of cyclin D1 and the up-regulation of Cdk inhibitor p21(Cip1/Waf1/Sdi1). 15d-PGJ2 was found to inhibit the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, which mediates cyclin D1 expression. Mitogenic stimulation of quiescent cells decreased the level of mRNA for the smooth muscle-specific myosin heavy-chain SM1, whereas this reduction was prevented by 15d-PGJ2. A long-term treatment of exponentially growing VSMCs with 15d-PGJ2 markedly elevated the mRNA level of SM1 and, moreover, induced SM2, another isoform expressed exclusively in mature VSMCs. 15d-PGJ2 also increased the expression levels of calponin-h1 and smooth muscle α-actin. These results suggest that 15d-PGJ2 induces G1 arrest by two distinct mechanisms and promotes VSMC differentiation.

本文言語英語
ページ(範囲)837-844
ページ数8
ジャーナルMolecular Pharmacology
58
4
DOI
出版ステータス出版済み - 1 1 2000
外部発表はい

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

フィンガープリント 「15-deoxy-Δ<sup>12,14</sup>-prostaglandin J<sub>2</sub> induces G<sub>1</sub> arrest and differentiation marker expression in vascular smooth muscle cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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