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Background: 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. Methods: 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. Results: 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. Conclusion: Curcumin reduced the transcription level of LTBP2 by inhibiting HIF‐1α, thereby inactivating NF‐κB pathway to alleviate Are‐induced OSF. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress is a common cellular stress response that is triggered by a variety of conditions that disturb cellular homeostasis, and induces cell apoptosis. Autophagy, an important and evolutionarily conserved mechanism for maintaining cellular homeostasis, is closely related to the apoptosis induced by ER stress. There are common upstream signaling pathways between autophagy and apoptosis induced by ER stress, including PERK/ATF4, IRE1α, ATF6, and Ca2+. Autophagy can not only block the induction of apoptosis by inhibiting the activation of apoptosis-associated caspase which could reduce cellular injury, but also help to induce apoptosis. In addition, the activation of apoptosis-related proteins can also inhibit autophagy by degrading autophagy-related proteins, such as Beclin-1, Atg4D, Atg3, and Atg5. Although the interactions of different autophagy- and apoptosis-related proteins, and also common upstream signaling pathways have been found, the potential regulatory mechanisms have not been clearly understood. In this review, we summarize the dual role of autophagy, and the interplay and potential regulatory mechanisms between autophagy and apoptosis under ER stress condition. [ABSTRACT FROM AUTHOR]