Metabolic Syndrome Induces Epigenetic Alterations in Mitochondria-Related Genes in Swine Mesenchymal Stem Cells.
Metabolic Syndrome Induces Epigenetic Alterations in Mitochondria-Related Genes in Swine Mesenchymal Stem Cells.
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自体骨髓间充质干/基质细胞（mesenchymal stem/stromal cells，MSCs）在多种疾病中具有重要的治疗作用。心血管危险因素可能损害MSC线粒体结构和功能，但其潜在机制尚不清楚。我们假设代谢综合征（MetS）诱导猪MSC中的ESTA相关基因的表观遗传学改变。猪饲喂瘦肉或MetS饮食（每种n = 6）16周。从皮下腹部脂肪收集MSC，并通过羟甲基化DNA免疫沉淀和下一代测序（hMeDIP-seq）分析未处理或用表观遗传调节剂维生素（Vit）-C处理的Lean-和MetS-MSC（各n = 3）中的Lean-和MetS-MSC中的线粒体相关基因（MitoCarta-2.0）的DNA羟甲基化（5 hmC）谱。使用DAVID 6.8进行具有差异5 hmC区域的基因的功能分析。线粒体结构（电子显微镜），氧化应激和膜电位进行了评估。hMeDIP-seq鉴定了MetS-MSC与Lean-MSC中具有较高hmC水平的172个峰（与103个线粒体基因相关）和具有较低hmC水平的416个峰（与165个线粒体基因相关）（≥2倍，p < 0.05）。MetS + MSC中具有较高5 hmC水平的基因主要涉及脂肪酸代谢，而具有较低5 hmC水平的基因与电子传递链活性相关。Vit-C增加线粒体抗氧化基因中的5 hmC水平，改善线粒体结构和膜电位，并降低氧化应激。MetS改变了猪MSC中的5 hmC水平的ESTA相关基因。Vit-C调节这些基因中的5 hmC水平，并保留MetS-MSCs中的线粒体结构和功能。这些观察结果可能有助于制定策略，以克服MetS对MSC的有害影响。
Autologous mesenchymal stem/stromal cells (MSCs) have demonstrated important therapeutic effects in several diseases. Cardiovascular risk factors may impair MSC mitochondrial structure and function, but the underlying mechanisms remain unknown. We hypothesized that metabolic syndrome (MetS) induces epigenetic alterations in mitochondria-related genes in swine MSCs. Pigs were fed a Lean or MetS diet (n = 6 each) for 16 weeks. MSCs were collected from subcutaneous abdominal fat, and DNA hydroxymethylation (5 hmC) profiles of mitochondria-related genes (MitoCarta-2.0) were analyzed by hydroxymethylated DNA immunoprecipitation and next-generation sequencing (hMeDIP-seq) in Lean- and MetS-MSCs untreated or treated with the epigenetic modulator vitamin (Vit)-C (n = 3 each). Functional analysis of genes with differential 5 hmC regions was performed using DAVID6.8. Mitochondrial structure (electron microscopy), oxidative stress, and membrane potential were assessed. hMeDIP-seq identified 172 peaks (associated with 103 mitochondrial genes) with higher and 416 peaks (associated with 165 mitochondrial genes) with lower 5 hmC levels in MetS-MSCs versus Lean-MSCs (≥2-fold, p < 0.05). Genes with higher 5 hmC levels in MetS + MSCs were primarily implicated in fatty acid metabolism, whereas those with lower 5 hmC levels were associated with electron transport chain activity. Vit-C increased 5 hmC levels in mitochondrial antioxidant genes, improved mitochondrial structure and membrane potential, and decreased oxidative stress. MetS alters 5 hmC levels of mitochondria-related genes in swine MSCs. Vit-C modulated 5 hmC levels in these genes and preserved mitochondrial structure and function in MetS-MSCs. These observations may contribute to development of strategies to overcome the deleterious effects of MetS on MSCs.
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影响因子：
3.7
作者：
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影响因子：
3.7
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4.8
作者：
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影响因子：
5.2
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影响因子：
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