Curcumin relieves arecoline-induced oral submucous fibrosis via inhibiting the LTBP2/NF-κB axis.

Abstract

Submucosal fibrosis (OSF) of the oral cavity is a chronic scarring disease. Arecoline (Are) is the driving factor for the occurrence and deterioration of OSF. Curcumin plays a vital anti-inflammatory role in Are-induced OSF development. However, its potential pharmacological mechanism needs to be elucidated. The relative molecular level was measured via qRT-PCR or Western blot. MTT assay, transwell assay and flow cytometry detected cell proliferation, migration, and apoptosis. The correlation between hypoxia-inducible factor-1α (HIF-1α) and LTBP2 promoter was confirmed through dual-luciferase reporter assay. ELISA was performed to detect inflammatory cytokines levels. Curcumin alleviated Are-induced oral mucosal fibroblast cells fibrosis by reducing oral mucosa fibroblasts viability, promoting cell apoptosis, suppressing cell migration, and down-regulating the levels of fibrosis markers and inflammatory factors. Curcumin relieved Are-induced OSF via inhibiting HIF-1α. Mechanically, HIF-1α bound to the promoter of LTBP2 to transcriptionally activated LTBP2. LTBP2 knockdown relieved Are-induced OSF, and curcumin down-regulated LTBP2 via inhibiting HIF-1α to relieve Are-induced OSF. Moreover, curcumin decreased NF-κB signal associated proteins via inhibiting LTBP2 to relieve Are-induced OSF. Curcumin reduced the transcription level of LTBP2 by inhibiting HIF-1α, thereby inactivating NF-κB pathway to alleviate Are-induced OSF.