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首页> 外文期刊>Clinical epigenetics. >Augmentation of histone deacetylase 3 (Emphasis Type="Italic"HDAC3/Emphasis) epigenetic signature at the interface of proinflammation and insulin resistance in patients with type 2 diabetes
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Augmentation of histone deacetylase 3 (Emphasis Type="Italic"HDAC3/Emphasis) epigenetic signature at the interface of proinflammation and insulin resistance in patients with type 2 diabetes

机译：2型糖尿病患者在炎症和胰岛素抵抗界面上的组蛋白脱乙酰基酶3（ HDAC3 ）表观遗传标记的增强

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class="Heading">Background id="Par1" class="Para">A role of proinflammation has been implicated in the pathogenesis of diabetes, but the up-stream regulatory signals and molecular signatures are poorly understood. While histone modifications such as changes in histone deacetylase (HDAC) are emerging as novel epigenetic biomarkers, there is lack of studies to demonstrate their clinical relevance in diabetes. Therefore, we investigated the extent of HDAC machinery and inflammatory signals in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes mellitus (T2DM) compared to control subjects. class="Heading">Results id="Par2" class="Para">HDAC3 activity was significantly (pa€‰a€‰0.05) increased in patients with T2DM compared to control subjects. While subtypes of HDACs were differentially expressed at their transcriptional levels in patients with type 2 diabetes, the most prominent observation is the significantly (pa€‰a€‰0.05) elevated messenger RNA (mRNA) levels of HDAC3. Expression levels of Sirt1 which represents the class III HDAC were decreased significantly in T2DM (pa€‰a€‰0.05). Plasma levels of both TNF-?± and IL-6 were significantly higher (pa€‰a€‰0.05) in patients with type 2 diabetes compared to control subjects. Among the proinflammatory mediators, the mRNA expression of MCP-1, IL1-?2, NF?oB, TLR2, and TLR4 were also significantly (pa€‰a€‰0.05) increased in T2DM. Transcriptional levels of DBC1 (deleted in breast cancer 1, which is a negative regulator of HDAC3) were seen significantly reduced in PBMCs from T2DM. Interestingly, HDAC3 activity/HDAC3 mRNA levels positively correlated to proinflammation, poor glycemic control, and insulin resistance. class="Heading">Conclusions id="Par3" class="Para">Striking message from this study is that while looking for anti-inflammatory strategies and drugs with novel mode of action for T2DM, discovering and designing specific inhibitors targeted to HDAC3 appears promising.
机译：class =“ Heading”>背景 id =“ Par1” class =“ Para”>促炎作用与糖尿病的发病机制有关，但上游调节信号和分子标志是知之甚少。尽管组蛋白修饰（例如组蛋白脱乙酰基酶（HDAC）的变化）正在作为新型表观遗传生物标志物出现，但仍缺乏研究证明其在糖尿病中的临床意义。因此，我们调查了2型糖尿病（T2DM）患者与对照组相比，外周血单个核细胞（PBMC）中HDAC机制和炎症信号的程度。 class =“ Heading”>结果 id =“ Par2” class =“ Para”> HDAC3 活动显着（ p a€‰ p a a <0.05） HDAC3 的RNA（mRNA）水平。在T2DM中，代表III类HDAC的Sirt1的表达水平显着降低（ p a <0.05）。与对照组相比，2型糖尿病患者的血浆TNF-α和IL-6含量均显着较高（ p a <0.05）。在促炎介质中，MCP-1，IL1-？2，NF？oB，TLR2和TLR4的mRNA表达也显着（ p a 0.05）在T2DM中增加。在来自T2DM的PBMC中，DBC1的转录水平（在HDAC3的负调节剂乳腺癌1中被删除）被显着降低。有趣的是， HDAC3 活性/ HDAC3 mRNA水平与促炎，血糖控制不良和胰岛素抵抗呈正相关。 class =“ Heading”>结论 id =“ Par3” class =“ Para”>这项研究的惊人信息是，在寻找抗炎策略和具有新型T2DM作用方式的药物时，发现并设计针对 HDAC3 看起来很有希望。

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