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.

Deodati, A., Argemi, J., Germani, D., Puglianiello, A., Alisi, A., De Stefanis, C., et al. (2018). The exposure to uteroplacental insufficiency is associated with activation of unfolded protein response in postnatal life. PLOS ONE, 13(6), e0198490 [10.1371/journal.pone.0198490].

The exposure to uteroplacental insufficiency is associated with activation of unfolded protein response in postnatal life

Deodati A.;Germani D.;Puglianiello A.;Cianfarani S.
2018-01-01

Abstract

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.
2018
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA
English
Animals; Aspartate-Ammonia Ligase; Disease Models, Animal; Endoplasmic Reticulum; Fatty Acids, Nonesterified; Female; Fetal Growth Retardation; Gene Expression Regulation; Glucose Tolerance Test; Heat-Shock Proteins; Leptin; Liver; Male; Metabolome; Pregnancy; RNA, Messenger; Rats; Rats, Sprague-Dawley; Unfolded Protein Response; X-Box Binding Protein 1
http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0198490&type=printable
Deodati, A., Argemi, J., Germani, D., Puglianiello, A., Alisi, A., De Stefanis, C., et al. (2018). The exposure to uteroplacental insufficiency is associated with activation of unfolded protein response in postnatal life. PLOS ONE, 13(6), e0198490 [10.1371/journal.pone.0198490].
Deodati, A; Argemi, J; Germani, D; Puglianiello, A; Alisi, A; De Stefanis, C; Ferrero, R; Nobili, V; Aragon, T; Cianfarani, S
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/232164
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