PKCδ mediates thrombin-augmented fibroblast-mediated collagen gel contraction

Qiuhong Fang, Lijun Mao, Tetsu Kobayashi, Xingqi Wang, Todd A Wyatt, Huijung Kim, Xiang-de Liu, Stephen I. Rennard

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4 Scopus citations

Abstract

Fibroblast-mediated collagen gel contraction has been used as an in vitro model of tissue remodeling. Thrombin is one of the mediators present in the milieu of airway inflammation and may be involved in airway tissue remodeling. We have previously reported that thrombin stimulates fibroblast-mediated collagen gel contraction partially through the PAR1/PKCε signaling pathway [Q. Fang, X. Liu, S. Abe, T. Kobayashi, X.Q. Wang, T. Kohyama, M. Hashimoto, T. Wyatt, S.I. Rennard, Thrombin induces collagen gel contraction partially through PAR1 activation and PKC-ε, Eur. Respir. J. 24 (2004) 918-924]. Here, we further report that the delta-isoform of PKC (PKCδ) is also activated by thrombin and involved in the thrombin-mediated augmentation of collagen gel contraction. Thrombin (10 nM) significantly increased PKCδ activity (over 5-fold increase after 15-30 min stimulation) and stimulated phosphorylation of PKCδ. Rottlerin, a PKCδ inhibitor, completely inhibited activation of PKCδ and partially blocked collagen gel contraction stimulated by thrombin. Similarly, PKCδ-specific siRNA significantly inhibited PKCδ activation without affecting PKCε expression and activation. Furthermore, suppression of PKCδ by siRNA resulted in partial blockade of thrombin-augmented collagen gel contraction. These results suggest that thrombin contributes to the tissue remodeling in inflammatory airways and lung diseases at least partially through both PKCδ and PKCε signaling.

Original languageEnglish (US)
Pages (from-to)1199-1203
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume369
Issue number4
DOIs
StatePublished - May 16 2008

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Keywords

  • Fibroblast
  • PKC
  • Tissue repair

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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