母体营养限制、子宫内生长受限和糖皮质激素暴露对体外培养的胎儿狒狒肝细胞中磷酸烯醇丙酮酸羧激酶-1表达的影响。
Effects of maternal nutrient restriction, intrauterine growth restriction, and glucocorticoid exposure on phosphoenolpyruvate carboxykinase-1 expression in fetal baboon hepatocytes in vitro.
作者信息
Li Cun, Shu Zhen-Ju, Lee Shuko, Gupta Madhulika B, Jansson Thomas, Nathanielsz Peter W, Kamat Amrita
机构信息
Center for Pregnancy and Newborn Research, University of Texas Health Science Center, San Antonio, TX, USA.
出版信息
J Med Primatol. 2013 Aug;42(4):211-9. doi: 10.1111/jmp.12048. Epub 2013 Apr 20.
Abstract
BACKGROUND
The objective of this study was to develop a cell culture system for fetal baboon hepatocytes and to test the hypotheses that (i) expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase-1 (PEPCK-1) is upregulated in hepatocytes isolated from fetuses of nutrient-restricted mothers (MNR) compared with ad libitum-fed controls (CTR), and (ii) glucocorticoids stimulate PEPCK-1 expression.
METHODS
Hepatocytes from 0.9G CTR and MNR fetuses were isolated and cultured. PEPCK-1 protein and mRNA levels in hepatocytes were determined by Western blot and quantitative PCR, respectively.
RESULTS
Fetuses of MNR mothers were intrauterine growth restricted (IUGR). Feasibility of culturing 0.9G fetal baboon hepatocytes was demonstrated. PEPCK-1 protein levels were increased in hepatocytes isolated from IUGR fetuses, and PEPCK-1 mRNA expression was stimulated by glucocorticoids in fetal hepatocytes.
CONCLUSIONS
Cultured fetal baboon hepatocytes that retain their in vivo phenotype provide powerful in vitro tools to investigate mechanisms that regulate normal and programmed hepatic function.
摘要
背景
本研究的目的是建立一种用于胎儿狒狒肝细胞的细胞培养系统，并检验以下假设：（i）与自由采食的对照胎儿（CTR）相比，从营养受限母亲（MNR）的胎儿分离出的肝细胞中糖异生酶磷酸烯醇丙酮酸羧激酶-1（PEPCK-1）的表达上调；（ii）糖皮质激素刺激PEPCK-1的表达。
方法
分离并培养来自0.9G CTR和MNR胎儿的肝细胞。分别通过蛋白质免疫印迹法和定量PCR测定肝细胞中PEPCK-1蛋白和mRNA水平。
结果
MNR母亲的胎儿出现宫内生长受限（IUGR）。证明了培养0.9G胎儿狒狒肝细胞的可行性。从IUGR胎儿分离出的肝细胞中PEPCK-1蛋白水平升高，糖皮质激素刺激胎儿肝细胞中PEPCK-1 mRNA的表达。
结论
保留其体内表型的培养胎儿狒狒肝细胞为研究调节正常和程序化肝功能的机制提供了强大的体外工具。
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