The exposure to uteroplacental insufficiency is associated with activation of unfolded protein response in postnatal life.
The exposure to uteroplacental insufficiency is associated with activation of unfolded protein response in postnatal life.
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DOI：
10.1371/journal.pone.0198490
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Cianfarani S
中科院分区：
文献类型：
--
作者：
Deodati A;Argemí J;Germani D;Puglianiello A;Alisi A;De Stefanis C;Ferrero R;Nobili V;Aragón T;Cianfarani S
早期生活事件与成年后易患慢性病有关。内质网(ER)动态平衡的紊乱激活了未折叠蛋白反应(UPR)，从而促进了代谢变化的发生。我们的目的是在宫内生长受限(IUGR)的动物模型中评估肝脏UPR。出生时IUGR大鼠肝脏X-box结合蛋白-1剪接(XBP1s)、内质网定位的DNAJ同源物(Erdj4)和Bip/GRP78-葡萄糖调节蛋白78(Bip；0.05)的表达显著增加。此外，IUGR仔鼠的糖异生基因和脂肪生成基因的表达显著上调(p<；0.05)。105日龄时，IUGR雄性大鼠的糖耐量显著降低(p<；0.01)。IUGR雄性成年大鼠肝脏XBP1s基因表达显著降低(p<；0.01)，双链RNA依赖的蛋白激酶样ER激酶(PERK)和天冬酰胺合成酶(ASNS)表达显著增加(p<；0.05)。IUGR大鼠出现肝局灶性脂肪变性和门脉周围纤维化。这些发现首次表明，胎儿暴露于子宫胎盘功能不全与肝脏UPR的激活有关，提示UPR信号可能在代谢风险中发挥作用。
Early life events are associated with the susceptibility to chronic diseases in adult life. Perturbations of endoplasmic reticulum (ER) homeostasis activate the unfolded protein response (UPR), which contributes to the development of metabolic alterations. Our aim was to evaluate liver UPR in an animal model of intrauterine growth restriction (IUGR). A significantly increased expression of X-box binding protein-1 spliced (XBP1s) mRNA (p<0.01), Endoplasmic Reticulum-localized DnaJ homologue (Erdj4) mRNA (p<0.05) and Bip/GRP78-glucose-regulated protein 78 (Bip) mRNA (p<0.05) was observed in the liver of IUGR rats at birth. Furthermore, the expression of gluconeogenesis genes and lipogenesis genes were significantly upregulated (p<0.05) in IUGR pups. At 105 d, IUGR male rats showed significantly reduced glucose tolerance (p<0.01). A significant decreased expression of XBP1s mRNA (p<0.01) and increased expression of double-stranded RNA-dependent protein kinase-like ER kinase (PERK) and Asparagine synthetase (ASNS) (p<0.05) was observed in the liver of IUGR male adult rats. Liver focal steatosis and periportal fibrosis were observed in IUGR rats. These findings show for the first time that fetal exposure to uteroplacental insufficiency is associated with the activation of hepatic UPR and suggest that UPR signaling may play a role in the metabolic risk.
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影响因子：
13.5
作者：
Wang, Bo;Majumder, Sarmila;Nuovo, Gerard;Kutay, Huban;Volinia, Stefano;Patel, Tushar;Schmittgen, Thomas D.;Croce, Carlo;Ghoshal, Kalpana;Jacob, Samson T.
通讯作者：
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作者：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.1107394108
发表时间：
2011-09-20
影响因子：
11.1
作者：
Mao, Ting;Shao, Mengle;Liu, Yong
通讯作者：
Liu, Yong
影响因子：
7.3
作者：
Mounir Z;Krishnamoorthy JL;Wang S;Papadopoulou B;Campbell S;Muller WJ;Hatzoglou M;Koromilas AE
通讯作者：
Koromilas AE