Liu Junsheng, Liu Jun, Duan Shan, Liu Liu, Zhang Guangwen, Peng Xichun
Department of Food Science and Engineering, Jinan University, No. 601 West Huangpu Avenue, Guangzhou, Guangdong 510632, P. R. China.
Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, Guangdong 510642, P. R. China.
J Agric Food Chem. 2020 Dec 30;68(52):15449-15459. doi: 10.1021/acs.jafc.0c06483. Epub 2020 Dec 15.
DNA methylation is an epigenetic event that plays critical roles in the pathogenesis, progression, and treatment of human diseases. In this study, we investigated the epigenetic mechanisms for polysaccharide (APS)-improved osteoporosis in a rat model. The results showed that APS significantly changed the DNA methylome in colonic epithelia with great efficiency. Gene set enrichment analysis (GSEA) based on differentially methylated sites (DMSs) revealed that APS caused promoter DNA methylation changes of genes associated with calcium homeostasis, osteoclast/osteoblast balance, Wnt signaling, and hormone-related processes. Further analysis showed high consistency of APS-induced gene methylomic changes in colonic epithelia and its effects on diabetes, virus infection, and wound healing, which had been reported already. Moreover, we suggested new functions and the involved mechanisms of APS in heart disease, neurological disorder, reproductive problem, and olfactory dysfunction. In this study, we offered epigenetic mechanisms for APS-improved osteoporosis. More importantly, we proposed and proved a reliable method to explore the beneficial effects of bioactive polysaccharides by studying DNA methylation changes at nonfocal sites. We firmly believed the promising prospects of this method for its great efficiency, rapidness, and economy in exploring possible beneficial or therapeutic effects of functional macromolecules with one single experiment.
DNA甲基化是一种表观遗传事件，在人类疾病的发病机制、进展和治疗中起着关键作用。在本研究中，我们在大鼠模型中研究了多糖（APS）改善骨质疏松症的表观遗传机制。结果表明，APS能高效地显著改变结肠上皮细胞的DNA甲基化组。基于差异甲基化位点（DMS）的基因集富集分析（GSEA）显示，APS导致了与钙稳态、破骨细胞/成骨细胞平衡、Wnt信号传导和激素相关过程相关基因的启动子DNA甲基化变化。进一步分析表明，APS诱导的结肠上皮细胞基因甲基化组变化与其对糖尿病、病毒感染和伤口愈合的影响具有高度一致性，这些已有报道。此外，我们提出了APS在心脏病、神经疾病、生殖问题和嗅觉功能障碍中的新功能及相关机制。在本研究中，我们提供了APS改善骨质疏松症的表观遗传机制。更重要的是，我们提出并证明了一种可靠的方法，即通过研究非重点部位的DNA甲基化变化来探索生物活性多糖的有益作用。我们坚信该方法在通过单次实验探索功能性大分子可能的有益或治疗作用方面具有高效、快速和经济的广阔前景。
