Thrombin activates Ras-CREB/ATF-1 signaling and stimulates c-fos, c-jun, and c-myc expression in human gingival fibroblasts

Chiu Po Chan, Mei Chi Chang, Ying-Jan Wang, Lin I. Chen, Yi Ling Tsai, Jang Jaer Lee, Hsi Wei Jia, Jiiang Huei Jeng

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Background: Protease-activated receptors (PARs) can be stimulated by thrombin and other proteases generated by periodontal pathogens. Activation of PARs in gingival fibroblasts (GFs) can modulate wound healing and inflammatory responses in gingival tissues. Methods: The mRNA expression of PARs and early responsive genes in GFs and other oral cells was studied by reverse transcription-polymerase chain reaction. Western blotting was used to study the activation of p38 and cAMP responsive element binding protein (CREB)/activating transcription factor (ATF)-1 as well as Ras. Results: GFs, dental pulp cells, and buccal mucosal fibroblasts expressed PAR-1 and -3 receptors, whereas gingival keratinocytes expressed PAR-1 and -2 receptors. Stimulation of GFs by thrombin rapidly activated Ras signaling and the phosphorylation of CREB/ATF-1 and p38. Thrombin also stimulated the expression of c-fos in GFs within 1 hour of exposure. Stimulation of c-jun mRNA expression showed biphasic responses with two peaks after 1 and 8 hours of exposure. Elevated c-myc expression in GFs by thrombin was noted after 2 hours of exposure. Moreover, the stimulation of c-fos and c-myc mRNA expression by thrombin can be attenuated by D-Phe-Pro-ArgCH 2Cl, a serine-proteinase inhibitor. Conclusions: PAR activation during gingival wounding or inflammation may stimulate Ras-CREB/ATF-1 signaling and c-fos, c-jun, and c-myc expression. Thismight be due to the proteinase activity of thrombin. These signaling events are important for wound healing and inflammatory responses in gingival tissues.

Original languageEnglish
Pages (from-to)1248-1254
Number of pages7
JournalJournal of periodontology
Volume79
Issue number7
DOIs
Publication statusPublished - 2008 Jul 1

All Science Journal Classification (ASJC) codes

  • Periodontics

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