Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 369, Issue 4, Pages 1199-1203Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.03.016
Keywords
fibroblast; PKC; tissue repair
Categories
Funding
- NHLBI NIH HHS [R01 HL064088-04, 1R01 HL-6408804] Funding Source: Medline
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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/PKC epsilon 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 PAR] activation and PKC-epsilon, Eur. Respir. J. 24 (2004) 918-924]. Here, we further report that the delta-isoform of PKC (PKC delta) is also activated by thrombin and involved in the thrombin-mediated augmentation of collagen gel contraction. Thrombin (10nM) significantly increased PKC delta activity (over 5-fold increase after 15-30 min stimulation) and stimulated phosphorylation of PKC delta. Rottlerin, a PKC delta inhibitor, Completely inhibited activation of PKC delta and partially blocked collagen gel contraction stimulated by thrombin. Similarly, PKC delta-specific siRNA significantly inhibited PKC delta activation without affecting PKC delta expression and activation. Furthermore, suppression of PKC delta 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 PKC delta and PKCE signaling. (C) 2008 Elsevier Inc. All rights reserved.
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