Thrombin induces collagen gel contraction partially through PAR1 activation and PKC-E

Q. Fang, X. Liu, S. Abe, T. Kobayashi, X. Q. Wang, T. Kohyama, M. Hashimoto, T. Wyatt, S. I. Rennard

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The ability of fibroblasts to contract three-dimensional collagen gels has been used as a in vitro model of the tissue contraction which characterises both normal repair and fibrosis. Among its actions, thrombin can activate the protease-activated receptor (PAR)1 and, thereby, stimulate inflammation and repair. The current study evaluated whether thrombin could stimulate fibroblast-mediated collagen gel contraction by activating PAR1 and whether its downstream signalling depends on protein kinase C (PKC)-E. Human foetal lung fibroblasts (HFL-1) were cultured in three-dimensional collagen gels and the area of the gels was measured by image analyser. Both thrombin and TFLLR, a selective PAR1 agonist, stimulated collagen gel contraction mediated by HFL-1. After RNA interference-mediated PAR1 knockdown in HFL-1, both thrombin and the PAR1 agonist-induced gel contraction were partially inhibited (by 22.4±2.2% and 17.6±5.6%, respectively). The gel contraction stimulated by thrombin was also reduced by a nonspecific PKC inhibitor and a calcium-independent PKC-E inhibitor. Both thrombin and TFLLR significantly increased PKC-E activity, and this effect was blocked by PAR1 knockdown. Thrombin stimulates collagen gel contraction at least partially through activation of protease-activated receptor 1 and protein kinase C-E, and may contribute to tissue remodelling in inflammatory airway and lung diseases.

Original languageEnglish (US)
Pages (from-to)918-924
Number of pages7
JournalEuropean Respiratory Journal
Volume24
Issue number6
DOIs
StatePublished - Dec 1 2004

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Keywords

  • Gel contraction
  • Protease-activated receptor
  • Protein kinase C-E
  • Short interfering RNA
  • Thrombin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Fang, Q., Liu, X., Abe, S., Kobayashi, T., Wang, X. Q., Kohyama, T., Hashimoto, M., Wyatt, T., & Rennard, S. I. (2004). Thrombin induces collagen gel contraction partially through PAR1 activation and PKC-E. European Respiratory Journal, 24(6), 918-924. https://doi.org/10.1183/09031936.04.00005704