Signaling mechanism of thrombin-induced gingival fibroblast-populated collagen gel contraction

Jiiang Huei Jeng, Wan Hong Lan, Juo Song Wang, Chiu Po Chan, Yuan Soon Ho, Po Hsuen Lee, Ying Jen Wang, Tong Mei Wang, Yi Jane Chen, Mei Chi Chang

研究成果: 雜誌貢獻文章同行評審

19 引文 斯高帕斯(Scopus)

摘要

1 Thrombin is activated during gingival tissue injury and inflammation. Thrombin (platelet)-rich plasma has been used for periodontal regeneration with success. Thrombin and other bacterial proteases also affect the functions of adjacent periodontal cells via stimulation of protease-activated receptors (PARs). 2 We noted that thrombin (0.1-2 U ml -1), human, and frog PAR-1 agonist peptide (20-240 μM) induced the gingival fibroblast (GF)-populated collagen gel contraction within 2 h of exposure. However, PAR-2, PAR-3, and PAR-4 agonist peptide (20-240 μM) showed little effect on collagen gel contraction. U73122 (phospholipase C inhibitor) and 2-APB (IP3 antagonist) were effective in inhibition of GF contraction. 3 Thrombin-induced GF contraction was inhibited by 5 mM EGTA (an extracellular calcium chelator) and verapamil (an L-type calcium channel blocker). In addition, W7 (10 and 25 μM, a calcium/calmodulin (CaM) inhibitor), ML-7 (50 μM, myosin light chain kinase (MLCK) inhibitor), and HA1077 (100 μM, Rho kinase inhibitor) completely inhibited the thrombin-induced collagen gel contraction. Thrombin also induced the phosphorylation of ERK1/ERK2 and elevated the Rho-GTP levels in GF. 4 However, U0126 only partially inhibited the thrombin-induced GF contraction. Similarly, wortmannin (100 nM), LY294002 (20 μM) (two PI3K inhibitor) and genistein also showed partial inhibition. Moreover, NAC was not able to suppress the GF contraction, as supported by the slight decrease in reactive oxygen species production in GF by thrombin. 5 Thrombin also stimulated metalloproteinase-2 (MMP-2) and MMP-3 production in GF. But addition of GM6001 or 1,10-phenanthroline, two MMP inhibitors, could not inhibit the thrombin-induced GF contraction. 6 These results indicate that thrombin is crucial in the periodontal inflammation and wound healing by promoting GF contraction. This event is mainly mediated via PAR-1 activation, PLC activation, extracellular calcium influx via L-type calcium channel, and the calcium/CaM-MLCK and Rho kinase activation pathway.

原文英語
頁(從 - 到)188-198
頁數11
期刊British Journal of Pharmacology
147
發行號2
DOIs
出版狀態已發佈 - 一月 2006

ASJC Scopus subject areas

  • Pharmacology

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