School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Int J Oral Sci. 2017 Mar;9(1):38-42. doi: 10.1038/ijos.2016.49. Epub 2017 Feb 24.
Oral submucous fibrosis (OSF) is a potentially malignant disorder that is characterized by a progressive fibrosis in the oral submucosa. Arecoline, an alkaloid compound of the areca nut, is reported to be a major aetiological factor in the development of OSF. Low-power laser irradiation (LPLI) has been reported to be beneficial in fibrosis prevention in different damaged organs. The aim of this study was to investigate the potential therapeutic effects of LPLI on arecoline-induced fibrosis. Arecoline-stimulated human gingival fibroblasts (HGFs) were treated with or without LPLI. The expression levels of the fibrotic marker genes alpha-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF/CCN2) were analysed by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) and western blots. In addition, the transcriptional activity of CCN2 was further determined by a reporter assay. The results indicated that arecoline increased the messenger RNA and protein expression of CCN2 and α-SMA in HGF. Interestingly, both LPLI and forskolin, an adenylyl cyclase activator, reduced the expression of arecoline-mediated fibrotic marker genes and inhibited the transcriptional activity of CCN2. Moreover, pretreatment with SQ22536, an adenylyl cyclase inhibitor, blocked LPLI's inhibition of the expression of arecoline-mediated fibrotic marker genes. Our data suggest that LPLI may inhibit the expression of arecoline-mediated fibrotic marker genes via the cAMP signalling pathway.
口腔黏膜下纤维性变(OSF)是一种潜在的恶性疾病,其特征是口腔黏膜下进行性纤维化。槟榔碱,槟榔果中的一种生物碱化合物,据报道是 OSF 发展的主要病因。低功率激光辐射(LPLI)已被报道在不同受损器官的纤维化预防中具有有益作用。本研究旨在探讨 LPLI 对槟榔碱诱导的纤维化的潜在治疗作用。用或不用 LPLI 处理槟榔碱刺激的人牙龈成纤维细胞(HGF)。通过定量实时逆转录聚合酶链反应(RT-PCR)和 Western blot 分析纤维化标记基因α-平滑肌肌动蛋白(α-SMA)和结缔组织生长因子(CTGF/CCN2)的表达水平。此外,通过报告基因测定进一步确定 CCN2 的转录活性。结果表明,槟榔碱增加了 HGF 中 CCN2 和α-SMA 的信使 RNA 和蛋白表达。有趣的是,LPLI 和 forskolin(一种腺苷酸环化酶激活剂)均可降低槟榔碱介导的纤维化标记基因的表达,并抑制 CCN2 的转录活性。此外,用腺苷酸环化酶抑制剂 SQ22536 预处理可阻断 LPLI 对槟榔碱介导的纤维化标记基因表达的抑制作用。我们的数据表明,LPLI 可能通过 cAMP 信号通路抑制槟榔碱介导的纤维化标记基因的表达。