Long non-coding RNA expression profile in the kidneys of male, low birth weight rats exposed to maternal protein restriction at postnatal day 1 and day 10.

Long non-coding RNA expression profile in the kidneys of male, low birth weight rats exposed to maternal protein restriction at postnatal day 1 and day 10.
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出生后第 1 天和第 10 天受到母体蛋白质限制的雄性低出生体重大鼠肾脏中的长非编码 RNA 表达谱

DOI:
10.1371/journal.pone.0121587
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Feng X
Feng X
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li Y;Wang X;Li M;Pan J;Jin M;Wang J;Li X;Feng X

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长链非编码RNA(longnon-codingRNA,lncRNA)参与多种生物学功能,在多种疾病中异常表达,是出生后发育所必需的。在这项研究中,我们的目的是调查lncRNA的低出生体重(LBW)大鼠减少肾单位禀赋的限制母亲的蛋白质摄入量。肾单位禀赋减少导致的LBW是成年期高血压和终末期肾病的危险因素。方法取妊娠期和哺乳期低蛋白饲料喂养的LBW大鼠及出生后第1天(p1)和第10天(p10)正常蛋白饲料喂养的母鼠所生的正常对照大鼠的肾脏。在p10时计数肾脏中的肾小球总数。使用Agilent Rat lncRNA Array通过测序和筛选分析lncRNA表达谱。这些lncRNA的定量实时PCR(qRT-PCR)分析证实了一些基因的身份。结果LBW大鼠p10时每个肾脏的肾小球总数显著低于对照组。两组间共有42个lncRNA被鉴定为显著差异表达,倍数变化≥2.0。根据差异表达的lncRNA与肾脏发育相关的mRNA之间的相关性分析,我们随机选择了一些lncRNA用于在p1和p10两个时间点的LBW和对照肾脏之间的比较分析,使用qRT-PCR。与对照组相比,在p1和p10时,LBW大鼠中与丝裂原活化蛋白激酶4的mRNA表达显著相关的三种lncRNA(TCONS_00014139、TCONS_00014138和TCONS_00017119)表达异常。结论LBW大鼠肾单位发育过程中LncRNA表达异常,提示LncRNA可能参与了肾单位发育受损。
Background Long non-coding RNAs (lncRNAs), which are involved in a variety of biological functions and aberrantly expressed in many types of diseases, are required for postnatal development. In this study, we aimed to investigate the lncRNA profiles in low birth weight (LBW) rats with reduced nephron endowment induced by the restriction of maternal protein intake. LBW by reduced nephron endowment is a risk factor for hypertension and end-stage renal disease in adulthood. Methods Kidneys were obtained from LBW rats fed a low-protein diet throughout gestation and lactation as well as from normal control rats born from dams fed normal protein diets at postnatal day 1 (p1) and 10 (p10). The total number of glomeruli in the kidneys was counted at p10. LncRNA expression profiles were analyzed by sequencing and screening using the Agilent Rat lncRNA Array. Quantitative real-time PCR (qRT-PCR) analysis of these lncRNAs confirmed the identity of some genes. Results The total number of glomeruli per kidney at p10 was significantly lower in LBW rats than in controls. A total of 42 lncRNAs were identified to be significantly differentially expressed, with fold-changes ≥2.0, between the two groups. According to correlation analysis between the differentially expressed lncRNAs and mRNAs involved in kidney development, we randomly selected a number of lncRNAs for comparison analysis between LBW and control kidneys at the two time-points, p1 and p10, using qRT-PCR. Three lncRNAs (TCONS_00014139, TCONS_00014138, and TCONS_00017119), which were significantly correlated with the mRNA expression of mitogen-activated protein kinase 4, were aberrantly expressed in LBW rats, compared with controls, at both p1 and p10. Conclusions LncRNAs are aberrantly expressed in the kidneys of LBW rats, compared with controls, during nephron development, which indicates that lncRNAs might be involved in impaired nephron endowment.
DOI: 10.1371/journal.pgen.1002841
发表时间: 2012
期刊: PLoS genetics
影响因子: 4.5
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发表时间: 2011-09-15
影响因子: 10.5
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