Impaired autophagy flux by lncRNA NEAT1 is critical for inflammation factors production in human periodontal ligament stem cells with nicotine treatment

Abstract

Background and Objectives Periodontitis is the top reason for tooth loss, and smoking significantly increases severe periodontitis risk. Defective autophagy has been reported to play a vital role in periodontitis. This study aimed to elucidate the relationship between autophagy and inflammation factors production in nicotine‐treated periodontal ligament stem cells (PDLSCs) and the underlying mechanism. Methods In this study, transmission electron microscopy, immunofluorescence, and the mCherry‐GFP‐LC3 plasmid were used to study autophagy flux. The gene levels of inflammation factors and long noncoding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) were detected by quantitative real‐time PCR (qRT‐PCR). Western blot was performed to assess the protein levels of autophagic markers and α7 nicotinic acetylcholine receptor (α7nAChR). Results We found that nicotine impaired autophagosome‐lysosome fusion and lysosome functions to block autophagy flux, contributing to inflammatory factors production in nicotine‐treated PDLSCs. Moreover, nicotine upregulated NEAT1 by activating α7nAChR. NEAT1 decreased autophagy flux by downregulating syntaxin 17 (STX17). Conclusion Our data indicate that NEAT1‐decreased autophagy flux is pivotal for inflammation factors production in nicotine‐treated PDLSCs.

Bioinformatics-based approach to construct a ceRNA network between periodontitis and hereditary gingival fibroplasia

“…Additionally, lncRNA KCNQ1OT1, nuclear enriched abundant transcript 1 (NEAT1), lncRNA LRRC75A-AS1, and HELLPAR are key long non-coding RNAs involved in our ceRNA network to bridge the connection of HGF and periodontitis. KCNQ1OT1 (potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1), a crucial lncRNA in our ceRNA network, is involved in regulating lipid metabolism, atherosclerosis, and in ammation [82]. LncRNA KCNQ1OT1 regulated high glucose-induced proliferation, oxidative stress, ECM accumulation, and in ammation in human glomerular mesangial (HGMC) cells via the miR-147a/SOX6 axis in diabetic nephropathy (DN) [83], LncRNA KCNQ1OT1 can also target miR-214, and regulate ALP, BMP2, Runx2, OPN, and OCN in osteogenesis and related disorders, which may include osteoporosis and periodontitis [84].…”

Nicotine: From Discovery to Biological Effects

“…Nicotine-induced NEAT1 upregulation results in the suppression of its functional target gene, STX17. This phenomenon contributes to the blockage of autophagy flux and the production of inflammation factors within human periodontal ligament stem cells (PDLSCs) [125]. Given the role played by nicotine in the proliferation of human lung tumor cells, a thorough ultrastructural analysis of the effects caused by nicotine in these cells is important.…”

Programmed cell death of periodontal ligament cells

“…In PDLSCs, nicotine has also been shown to impair autophagosome‐lysosome fusion and lysosomal function to block autophagic flux, thereby upregulating the synthesis of inflammatory cytokines and exacerbating periodontal inflammation (Zhang et al, 2023). In addition, studies have demonstrated that nicotine can induce apoptosis of PDLSCs by activating nicotine acetylcholine receptors (nAChRs), resulting in cytotoxic effects (Kim et al, 2012).…”