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-Jan Wang, Tong Mei Wang, Yi Jane Chen, Mei Chi Chang

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Abstract

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.

Original languageEnglish
Pages (from-to)188-198
Number of pages11
JournalBritish Journal of Pharmacology
Volume147
Issue number2
DOIs
Publication statusPublished - 2006 Jan 1

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Thrombin
Collagen
Fibroblasts
Gels
PAR-1 Receptor
Myosin-Light-Chain Kinase
L-Type Calcium Channels
rho-Associated Kinases
Calmodulin
Calcium
Proteinase-Activated Receptors
PAR-2 Receptor
Inflammation
Peptides
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Platelet-Rich Plasma
Matrix Metalloproteinase Inhibitors
Genistein
Egtazic Acid
Matrix Metalloproteinase 2

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Jeng, J. H., Lan, W. H., Wang, J. S., Chan, C. P., Ho, Y. S., Lee, P. H., ... Chang, M. C. (2006). Signaling mechanism of thrombin-induced gingival fibroblast-populated collagen gel contraction. British Journal of Pharmacology, 147(2), 188-198. https://doi.org/10.1038/sj.bjp.0706462
Jeng, Jiiang Huei ; Lan, Wan Hong ; Wang, Juo Song ; Chan, Chiu Po ; Ho, Yuan Soon ; Lee, Po Hsuen ; Wang, Ying-Jan ; Wang, Tong Mei ; Chen, Yi Jane ; Chang, Mei Chi. / Signaling mechanism of thrombin-induced gingival fibroblast-populated collagen gel contraction. In: British Journal of Pharmacology. 2006 ; Vol. 147, No. 2. pp. 188-198.
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abstract = "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.",
author = "Jeng, {Jiiang Huei} and Lan, {Wan Hong} and Wang, {Juo Song} and Chan, {Chiu Po} and Ho, {Yuan Soon} and Lee, {Po Hsuen} and Ying-Jan Wang and Wang, {Tong Mei} and Chen, {Yi Jane} and Chang, {Mei Chi}",
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Jeng, JH, Lan, WH, Wang, JS, Chan, CP, Ho, YS, Lee, PH, Wang, Y-J, Wang, TM, Chen, YJ & Chang, MC 2006, 'Signaling mechanism of thrombin-induced gingival fibroblast-populated collagen gel contraction', British Journal of Pharmacology, vol. 147, no. 2, pp. 188-198. https://doi.org/10.1038/sj.bjp.0706462

Signaling mechanism of thrombin-induced gingival fibroblast-populated collagen gel contraction. / Jeng, Jiiang Huei; Lan, Wan Hong; Wang, Juo Song; Chan, Chiu Po; Ho, Yuan Soon; Lee, Po Hsuen; Wang, Ying-Jan; Wang, Tong Mei; Chen, Yi Jane; Chang, Mei Chi.

In: British Journal of Pharmacology, Vol. 147, No. 2, 01.01.2006, p. 188-198.

Research output: Contribution to journalArticle

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AU - Jeng, Jiiang Huei

AU - Lan, Wan Hong

AU - Wang, Juo Song

AU - Chan, Chiu Po

AU - Ho, Yuan Soon

AU - Lee, Po Hsuen

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AU - Wang, Tong Mei

AU - Chen, Yi Jane

AU - Chang, Mei Chi

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N2 - 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.

AB - 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.

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