title: Arecoline stimulated early growth response-1 production in human buccal fibroblasts: suppression by epigallocatechin-3-gallate.
abstract: BACKGROUND
  Early growth response-1 (Egr-1) protein plays an important role in many human fibrotic diseases. Areca nut chewing is the most important risk factor of oral submucous fibrosis (OSF).
  
  
  METHODS
  Egr-1 protein expression in OSF was examined using antibody to Egr-1. Arecoline-induced Egr-1 expression and its signaling pathways were assessed by Western blot analyses in human buccal mucosal fibroblasts (BMFs).
  
  
  RESULTS
  Elevated Egr-1 staining was observed in epithelial cells, fibroblast, and inflammatory cells in 7 of 10 OSF cases. Arecoline, a main alkaloid found in the areca nut, stimulated Egr-1 synthesis in BMFs. Pretreatment with antioxidant N-acetyl-L-cysteine, c-Jun NH2-terminal kinase inhibitor SP600125, and extracellular signal-regulated kinase inhibitor PD98059 significantly reduced arecoline-induced Egr-1 synthesis. Epigallocatechin-3-gallate (EGCG) inhibited arecoline-induced Egr-1 synthesis and collagen gel contraction in a dose-responsive manner.
  
  
  CONCLUSIONS
  Constitutive Egr-1 expression during areca nut chewing may play a role in the pathogenesis of OSF. EGCG could be a good candidate for prevention or treatment of OSF.
authors.affiliation: School of Dentistry, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Hsieh
authors.forename: Hsin-Ming
authors.initials: HM
authors.lastname: Chen
authors.forename: Jenny Zwei-Chieng
authors.initials: JZ
authors.lastname: Chang
authors.forename: Chun-Pin
authors.initials: CP
authors.lastname: Chiang
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Deng
authors.forename: Mark Yen-Ping
authors.initials: MY
authors.lastname: Kuo
mesh_terms: D001115:Arecoline / Q000494:pharmacology*; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002610:Cheek; D018679:Cholinergic Agonists / Q000494:pharmacology*; D051766:Early Growth Response Protein 1 / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D009061:Mouth Mucosa / Q000166:cytology* / Q000378:metabolism; D009914:Oral Submucous Fibrosis / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018679:Cholinergic Agonists; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D001115:Arecoline; D002392:Catechin; C045651:epigallocatechin gallate
keywords: arecoline; early growth response-1 (Egr-1); epigallocatechin-3-gallate (EGCG); fibroblast; oral submucous fibrosis