Arecoline Enhances Phosphodiesterase 4A Activity to Promote Transforming Growth Factor-β-Induced Buccal Mucosal Fibroblast Activation via cAMP-Epac1 Signaling Pathway.

ABSTRACT: Chewing areca nut (betel quid) is strongly associated with oral submucous fibrosis (OSF), a pre-cancerous lesion. Among the areca alkaloids, arecoline is the main agent responsible for fibroblast proliferation; however, the specific molecular mechanism of arecoline affecting the OSF remains unclear. The present study revealed that arecoline treatment significantly enhanced Transforming growth factor-β (TGF-β)-induced buccal mucosal fibroblast (BMF) activation and fibrotic changes. Arecoline interacts with phosphodiesterase 4A (PDE4A) to exert its effects through modulating PDE4A activity but not PDE4A expression. PDE4A silence reversed the effects of arecoline on TGF-β-induced BMFs activation and fibrotic changes. Moreover, the exchange protein directly activated by cAMP 1 (Epac1)-selectiv

SUBMITTER: Zhang B 

PROVIDER: S-EPMC8606562 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature