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• W1125422980 endingPage "1631" @default.
• W1125422980 startingPage "1622" @default.
• W1125422980 abstract "Betaine, which donates methyl groups through methionine metabolism for DNA and protein methylation, is critical for epigenetic gene regulation, especially during fetal development. Here we fed gestational sows with control or betaine supplemented diets (3 g/kg) throughout the pregnancy to explore the effects of maternal betaine on hepatic cell proliferation in neonatal piglets. Neonatal piglets born to betaine-supplemented sows demonstrated a reduction of cell number and DNA content in the liver, which was associated with significantly down-regulated hepatic expression of cell cycle regulatory genes, cyclin D2 (CCND2) and presenilin1 (PSEN1). Moreover, STAT3 binding to the promoter of CCND2 and PSEN1 was also lower in betaine-exposed piglets, accompanied by strong reduction of STAT3 mRNA and protein expression, along with its phosphorylation at Tyr705 and Ser727 residues. Also, prenatal betaine exposure significantly attenuated upstream kinases of STAT3 signaling pathway (phospho-ERK1/2, phospho-SRC and phospho-JAK2) in the livers of neonates. Furthermore, the repressed STAT3 expression in the liver of betaine-exposed piglets was associated with DNA hypermethylation and more enriched repression histone mark H3K27me3 on its promoter, together with significantly up-regulated expression of H3K27me3 and enhancer of zeste homolog 2 (EZH2) proteins, as well as miR-124a, which targets STAT3. Taken together, our results suggest that maternal dietary betaine supplementation during gestation inhibits hepatic cell proliferation in neonatal piglets, at least partly, through epigenetic regulation of hepatic CCND2 and PSEN1 genes via a STAT3-dependent pathway. These neonatal changes in cell cycle and proliferation regulation may lead to lower liver weight and hepatic DNA content at weaning." @default.
• W1125422980 created "2016-06-24" @default.
• W1125422980 creator A5011012416 @default.
• W1125422980 creator A5037147588 @default.
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• W1125422980 creator A5052944163 @default.
• W1125422980 creator A5076803183 @default.
• W1125422980 creator A5079286251 @default.
• W1125422980 date "2015-12-01" @default.
• W1125422980 modified "2023-09-24" @default.
• W1125422980 title "Maternal gestational betaine supplementation-mediated suppression of hepatic cyclin D2 and presenilin1 gene in newborn piglets is associated with epigenetic regulation of the STAT3-dependent pathway" @default.
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• W1125422980 doi "https://doi.org/10.1016/j.jnutbio.2015.08.007" @default.
• W1125422980 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26359029" @default.
• W1125422980 hasPublicationYear "2015" @default.
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