Prostacyclin analogs inhibit fibroblast contraction of collagen gels through the cAMP-PKA pathway

Koichiro Kamio, Xiangde Liu, Hisatoshi Sugiura, Shinsaku Togo, Tetsu Kobayashi, Shinsaku Kawasaki, Xingqi Wang, Lijun Mao, Youngsoo Ann, Cory Hogaboam, Myron L. Toews, Stephen I. Rennard

研究成果: Article査読

24 被引用数 (Scopus)

抄録

Prostacyclin is an arachidonic acid metabolite that modulates vascular tone within the lung. The current study evaluated the hypothesis that prostacyclin can also modulate tissue remodeling by affecting fibroblast-mediated contraction of extracellular matrix. To accomplish this, fibroblasts were cultured in three-dimensional native type I collagen gels in the presence of prostacyclin analogs: carbaprostacyclin, iloprost, and beraprost. All three analogs significantly inhibited contraction of the three-dimensional collagen gels mediated by three different fibroblasts. All three analogs significantly inhibited fibronectin release and reduced fibroblast fibronectin mRNA expression. Addition of exogenous fibronectin restored the contractile activity to fibroblasts incubated in the presence of all three analogs. Iloprost and beraprost significantly activated cAMP-dependent protein kinase-A (PKA), and an action through this pathway was con firmed by blockade of the inhibitory effect on contraction and fibronectin release with the PKA inhibitor KT-5720. In contrast, carbaprostacyclin, which is not as selective for the prostacyclin (IP) receptor, did not activate PKA, and its effects on contraction and fibronectin release were not fully blocked by KT-5720. Finally, the cAMP analogs N 6-Benzoyl- (6-Bnz-) cAMP and dibutyryl-cAMP inhibited contraction, and this contrasted with the activity of an Epac selective agonist 8-pCPT-2′-O-Me-cAMP, which had no effect. Taken together, these results indicate that prostacyclin, acting through the IP receptor and by activating PKA, can lead to inhibition of fibronectin release and can subsequently inhibit fibroblast-mediated collagen gel contraction. The ability of prostacyclin to modulate fibroblast function suggests that prostacyclin can contribute to tissue remodeling.

本文言語English
ページ(範囲)113-120
ページ数8
ジャーナルAmerican journal of respiratory cell and molecular biology
37
1
DOI
出版ステータスPublished - 2007 7月
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 呼吸器内科
  • 臨床生化学
  • 細胞生物学

フィンガープリント

「Prostacyclin analogs inhibit fibroblast contraction of collagen gels through the cAMP-PKA pathway」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。

引用スタイル