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首页> 外文学位 >Intrauterine growth restriction alters the epigenetic profile and decreases RNA of stearoyl CoA desaturase in newborn rat lung.
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Intrauterine growth restriction alters the epigenetic profile and decreases RNA of stearoyl CoA desaturase in newborn rat lung.

机译：宫内生长限制改变新生大鼠肺中的表观遗传学特征并降低硬脂酰辅酶A去饱和酶的RNA。

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摘要

Intrauterine growth restriction (IUGR) is associated with impaired lung development and function. Lung function is impaired in IUGR rats, in part, by altered surfactant composition. The lipid profile in lungs determines surfactant lipid composition. Our IUGR rats have decreased lung palmitoleic acid (16:1). Stearoyl CoA Desaturase (SCD), the rate-limiting enzyme in synthesis of palmitoleic acid, is a target of transcription factor peroxisome proliferator activated receptor gamma (PPARgamma) and is susceptible to transcriptional regulation through epigenetic modifications. There are a number of genes in the lung that show altered mRNA levels in association with decreased PPARgamma levels and epigenetic modifications in the presence of IUGR. The effect of IUGR on the epigenetic profile of SCD as well as SCD mRNA and protein levels in the newborn rat lung is unknown. We hypothesize that IUGR will be associated with reduced SCD mRNA and protein levels consistent with the previously observed decrease in PPARgamma levels in the lungs of d0 rat pups. We further hypothesize that there will be gender-specific changes in the epigenetic profile along the length of the SCD gene.;This hypothesis was tested using a uteroplacental insufficiency (UPI) model of IUGR in rats. Whole lung tissue was harvested at birth (d0) and used to assess SCD mRNA and protein levels by RT-PCR and western blot analysis. Epigenetic modifications (H3K14Ac and H3K36Me3) were assessed along the SCD gene using chromatin immunoprecipitation (ChIP).;Results showed that, in control lungs females have 153% higher SCD mRNA than males (p=0.005). A consistent decrease in SCD mRNA levels was found in both male and female IUGR rats at birth relative to controls (p=0.009, p=0.0023). H3K14Ac was increased at SCD exon 4 in IUGR females to 210% of the level detected in gender-matched controls (p=0.037). H3K3Me3 was decreased at SCD exon 4 in IUGR males by 43% (p=0.044) and at SCD 3'UTR in IUGR females by 65% relative to gender-matched controls (p=0.036). There was no change in SCD protein levels in IUGR rats at birth. In conclusion IUGR is associated with decreased SCD mRNA levels and gender-specific changes to the epigenetic profile along the SCD gene.
机译：宫内生长受限（IUGR）与肺发育和功能受损有关。 IUGR大鼠的肺功能受损，部分原因是表面活性剂组成改变。肺中的脂质分布决定了表面活性剂的脂质组成。我们的IUGR大鼠的肺棕榈油酸含量降低了（16：1）。硬脂酰CoA去饱和酶（SCD）是棕榈油酸合成中的限速酶，是转录因子过氧化物酶体增殖物激活受体γ（PPARgamma）的靶标，并且易于通过表观遗传修饰进行转录调控。在IUGR存在下，肺中有许多基因显示mRNA水平改变与PPARγ水平降低和表观遗传修饰有关。 IUGR对新生大鼠肺中SCD的表观遗传学谱以及SCD mRNA和蛋白水平的影响尚不清楚。我们假设IUGR将与SCD mRNA和蛋白质水平降低相关，这与先前观察到的d0大鼠幼崽肺中PPARgamma水平的降低相一致。我们进一步假设，沿SCD基因的长度，表观遗传分布将发生性别特异性变化。该假说是使用IUGR的子宫胎盘功能不全（UPI）模型在大鼠中测试的。在出生时（d0）收集整个肺组织，并通过RT-PCR和Western blot分析将其用于评估SCD mRNA和蛋白水平。使用染色质免疫沉淀法（ChIP）评估了SCD基因的表观遗传修饰（H3K14Ac和H3K36Me3）。结果表明，在对照肺中，女性的SCD mRNA比男性高153％（p = 0.005）。与对照组相比，雄性和雌性IUGR大鼠在出生时均发现SCD mRNA水平持续降低（p = 0.009，p = 0.0023）。在IUGR女性中，SCD外显子4的H3K14Ac升高至性别匹配对照中检测到的水平的210％（p = 0.037）。与性别匹配的对照相比，IUGR男性中SCD外显子4的H3K3Me3降低了43％（p = 0.044），IUGR女性中SCD 3'UTR降低了65％（p = 0.036）。 IUGR大鼠出生时SCD蛋白水平没有变化。总之，IUGR与SCD mRNA水平降低和沿SCD基因的表观遗传特性的性别特异性变化有关。

著录项

  • 作者

    Riederer, Allison Beran.;

  • 作者单位

    The University of Utah.;

  • 授予单位 The University of Utah.;
  • 学科 Nutrition.;Molecular biology.
  • 学位 M.S.
  • 年度 2012
  • 页码 35 p.
  • 总页数 35
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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