title: PKCdelta mediates thrombin-augmented fibroblast-mediated collagen gel contraction.
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/PKCepsilon 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-epsilon, Eur. Respir. J. 24 (2004) 918-924]. Here, we further report that the delta-isoform of PKC (PKCdelta) is also activated by thrombin and involved in the thrombin-mediated augmentation of collagen gel contraction. Thrombin (10nM) significantly increased PKCdelta activity (over 5-fold increase after 15-30min stimulation) and stimulated phosphorylation of PKCdelta. Rottlerin, a PKCdelta inhibitor, completely inhibited activation of PKCdelta and partially blocked collagen gel contraction stimulated by thrombin. Similarly, PKCdelta-specific siRNA significantly inhibited PKCdelta activation without affecting PKCepsilon expression and activation. Furthermore, suppression of PKCdelta 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 PKCdelta and PKCepsilon signaling.
authors.affiliation: Beijing Shijitan Hospital, Peking University, Beijing, China.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Fang
authors.forename: Lijun
authors.initials: L
authors.lastname: Mao
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Xingqi
authors.initials: X
authors.lastname: Wang
authors.forename: Todd A
authors.initials: TA
authors.lastname: Wyatt
authors.forename: Huijung
authors.initials: H
authors.lastname: Kim
authors.forename: Xiangde
authors.initials: X
authors.lastname: Liu
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Rennard
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D018929:Cell Culture Techniques; D003094:Collagen / Q000737:chemistry; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology*; D005782:Gels / Q000737:chemistry; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011658:Pulmonary Fibrosis / Q000201:enzymology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000098:Acetophenones; D001578:Benzopyrans; D005782:Gels; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D003094:Collagen; C085746:rottlerin; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D013917:Thrombin