Chen Qiang, Liu Shuiping, Zhang Yun, Zheng Da, Ma Qianqian, Wei Jianrui, Liu Xiaoshan, Hu Dandan, Xie Bo
Department of Stomatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Faculty of Forensic Medicine, Zhongshan School of Medicine, and Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Sun Yat-Sen University, Guangzhou, China.
Odontology. 2025 Aug 18. doi: 10.1007/s10266-025-01172-8.
Oral submucous fibrosis (OSF) is a precancerous oral condition, with betel quid chewing and smoking identified as potential risk factors. However, the relationship between these factors, particularly their interaction, remains inconclusive. In this study, we observed that low-dose nicotine exposure (< 500 nM) increased arecoline-induced proliferation of human oral mucosa fibroblasts, whereas high doses of nicotine (1000 nM and 5000 nM) inhibited fibroblast proliferation. Our experiments elucidated the essential role of the Egr-1/Wnt5a pathway in nicotine-induced fibroblast proliferation. Nicotine amplified the impact of arecoline by further activating the Egr-1/Wnt5a pathway. Upon exposure to nicotine (250 nM) with or without arecoline, the expression of Egr-1 mRNA remained unaltered, yet Egr-1 and Wnt5a protein levels increased. Interestingly, Egr-1 exhibited enhanced stability in nicotine-treated cells, regardless of the presence of arecoline. Thus, it is evident that low-dose nicotine promotes arecoline-induced proliferation of human oral mucosa fibroblasts by enhancing the stability of the Egr-1 protein.
口腔黏膜下纤维化（OSF）是一种癌前口腔疾病，嚼槟榔和吸烟被确定为潜在风险因素。然而，这些因素之间的关系，尤其是它们的相互作用，仍无定论。在本研究中，我们观察到低剂量尼古丁暴露（<500 nM）会增加槟榔碱诱导的人口腔黏膜成纤维细胞增殖，而高剂量尼古丁（1000 nM和5000 nM）则抑制成纤维细胞增殖。我们的实验阐明了Egr-1/Wnt5a通路在尼古丁诱导的成纤维细胞增殖中的关键作用。尼古丁通过进一步激活Egr-1/Wnt5a通路增强了槟榔碱的影响。在暴露于含或不含槟榔碱的尼古丁（250 nM）后，Egr-1 mRNA的表达保持不变，但Egr-1和Wnt5a蛋白水平增加。有趣的是，无论是否存在槟榔碱，Egr-1在尼古丁处理的细胞中都表现出增强的稳定性。因此，很明显，低剂量尼古丁通过增强Egr-1蛋白的稳定性促进槟榔碱诱导的人口腔黏膜成纤维细胞增殖。
