Shen Yifen, Liu Chao, Yang Tao, Tang Ying, Shen Yihang, Gu Yongchun
Central Laboratory, Ninth People's Hospital of Suzhou, Soochow University, Suzhou, Jiangsu, 215200, China.
Department of Dentistry, Ninth People's Hospital of Suzhou, Soochow University, Suzhou, Jiangsu, 215200, China.
Environ Pollut. 2023 Apr 15;323:121307. doi: 10.1016/j.envpol.2023.121307. Epub 2023 Feb 15.
The potential toxicities and threats of electronic cigarettes (E-cigs) on periodontal health remain elusive. Gingival mesenchymal stem cells (GMSCs) and periodontal ligament stem cells (PDLSCs) contribute to cell differentiation and regeneration for periodontium as well as inflammatory modulation. However, the effects of E-cig exposure on periodontal tissues, particularly GMSCs and PDLSCs, and the underlying epigenetic mechanisms remain largely unknown. In this study, we conducted RNA-seq analysis to examine the transcriptome of human GMSCs and PDLSCs exposed to four types of E-cigs (aerosol and liquid with tobacco and menthol flavor) and conventional tobacco smoke in vitro. Our results showed that E-cig exposure primarily impacted the immunoregulation and inflammatory responses to pathogenic microorganisms in GMSCs, and the microenvironment, differentiation and response to corticosteroid in PDLSCs, which were significantly different from the damage effects caused by tobacco smoke. Additionally, we discovered a large number of differentially expressed non-coding RNAs among the different E-cig exposure methods and flavors. We also noticed that in GMSCs, CXCL2 was especially down-regulated by E-cig aerosol exposure whereas up-regulated by E-liquid exposure compared to control. Of note, the enhancer elements near CXCL2 and other genes located at Chromosome 4 contributed to the transcription activity of these genes, and KDM6B was remarkably elevated in response to E-liquid exposure. Lastly, we conducted ChIP-seq analysis to confirm that the elevated gene transcription by E-liquids was due to the weakened H3K27me3 at genome-wide enhancer elements in GMSCs, but not at promoter regions. Taken together, our results characterized the diverse gene expression profiles of GMSCs and PDLSCs in response to E-cigs with different exposure methods and flavors in vitro, and indicated a novel mechanism of KDM6B-mediated H3K27me3 on enhancers for gene transcription regulation. Our data could be served as a resource for emphasizing the understanding of E-cigs in periodontal health.
电子烟对牙周健康的潜在毒性和威胁仍不明确。牙龈间充质干细胞（GMSCs）和牙周膜干细胞（PDLSCs）有助于牙周组织的细胞分化和再生以及炎症调节。然而，电子烟暴露对牙周组织，特别是GMSCs和PDLSCs的影响以及潜在的表观遗传机制在很大程度上仍不清楚。在本研究中，我们进行了RNA测序分析，以检测体外暴露于四种类型电子烟（含烟草和薄荷醇口味的气溶胶和烟液）及传统烟草烟雾中的人GMSCs和PDLSCs的转录组。我们的结果表明，电子烟暴露主要影响GMSCs中对致病微生物的免疫调节和炎症反应，以及PDLSCs中的微环境、分化和对皮质类固醇的反应，这与烟草烟雾造成的损伤效应显著不同。此外，我们在不同的电子烟暴露方法和口味中发现了大量差异表达的非编码RNA。我们还注意到，在GMSCs中，与对照相比，电子烟气溶胶暴露使CXCL2尤其下调，而烟液暴露则使其上调。值得注意的是，位于4号染色体上的CXCL2和其他基因附近的增强子元件有助于这些基因的转录活性，并且KDM6B在烟液暴露后显著升高。最后，我们进行了染色质免疫沉淀测序分析，以确认烟液引起的基因转录升高是由于GMSCs全基因组增强子元件处H3K27me3减弱，而非启动子区域。综上所述，我们的结果描绘了体外暴露于不同方法和口味电子烟时GMSCs和PDLSCs的多样基因表达谱，并表明了KDM6B介导的H3K27me3在增强子上对基因转录调控的新机制。我们的数据可作为增进对电子烟在牙周健康方面理解的资源。
