MISC

2007年10月

Sphingosine kinase 1 regulates differentiation of human and mouse lung fibroblasts mediated by TGF-beta 1

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
  • Yuko Kono
  • ,
  • Teruaki Nishiuma
  • ,
  • Yoshihiro Nishimura
  • ,
  • Yoshikazu Kotani
  • ,
  • Taro Okada
  • ,
  • Shun-ichi Nakamura
  • ,
  • Mitsuhiro Yokoyama

37
4
開始ページ
395
終了ページ
404
記述言語
英語
掲載種別
DOI
10.1165/rcmb.2007-0065OC
出版者・発行元
AMER THORACIC SOC

Transforming growth factor beta (TGF-beta) contributes to the progression of pulmonary fibrosis through up-regulation of alpha-smooth muscle actin (alpha-SMA) as lung myofibroblast differentiation. Bioactive sphingosine 1-phosphate (S1P) has been shown to mimic TGF-beta signals; however, the function of S1P in lung fibrotic process has not been well documented. We found, in a mouse model of bleomycin lung fibrosis, that SPHIK1 and alpha-SMA were colocalized within lung fibrotic foci and that these expressions were significantly increased in primary cultured fibroblasts. Using human lung fibroblasts WI-38, we explored the rationale of sphingosine kinase(SPHK) with TGF-beta 1 stimulation. SPHK inhibitors and small interference RNA (siRNA) targeted SPHK1 decreased alpha-SMA and fibronectin expression up-regulated by TGF-beta 1. In the meantime, SPHK1 inhibition did not affect smad2 phosphorylation in response to TGF-beta 1. Then we examined whether S1P receptors transactivation may affect TGF-beta signals. siRNA against S1P(2) and S1P(3), but not S1P(1), reduced alpha-SMA expression as well as Y-27632, Rho kinase inhibitor. We also detected activation of Rho GTPase upon stimulation of TGF-beta 1 on the cell membrane where S1P(2) or S1P(3) was overexpressed. These data suggested that SPHK1 activation by TGF-beta 1 leads to Rho-associated myofibroblasts differentiation mediated by transactivated S1P receptors in the lung fibrogenic process.

Web of Science ® 被引用回数 : 110

リンク情報
DOI
https://doi.org/10.1165/rcmb.2007-0065OC
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000249898400005&DestApp=WOS_CPL
ID情報
  • DOI : 10.1165/rcmb.2007-0065OC
  • ISSN : 1044-1549
  • Web of Science ID : WOS:000249898400005

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