PKCdelta mediates thrombin-augmented fibroblast-mediated collagen gel contraction |
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Authors: | Fang Qiuhong Mao Lijun Kobayashi Tetsu Wang Xingqi Wyatt Todd A Kim Huijung Liu Xiangde Rennard Stephen I |
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Institution: | a Beijing Shijitan Hospital, Peking University, Beijing, China b The 3rd Hospital of Peking University, Beijing, China c Mie University of Graduate School of Medicine, Tsu City, Japan d University of Nebraska Medical Center, 985885 Nebraska Medical Center, Omaha, Nebraska 68198-5885, USA e Wonkwang University, Kunpo Medical Center, Seoul, Republic of Korea |
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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. |
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Keywords: | Fibroblast PKC Tissue repair |
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