Taurine improves the differentiation of neural stem cells in fetal rats with intrauterine growth restriction via activation of the PKA-CREB-BDNF signaling pathway

ABSTRACT Background Previous studies have revealed that dietary N-carbamylglutamate (NCG) and l-arginine (Arg) improve intestinal integrity, oxidative state, and immune function in Hu suckling lambs with intrauterine growth restriction (IUGR). Whether these treatments alter intestinal nutrient absorption is unknown. Objective The aim of this study was to determine the influence of dietary NCG and Arg treatment during the suckling period on intestinal amino acid (AA) absorption, alterations in the mechanistic target of rapamycin (mTOR) signaling pathway, and the abundance of AA and peptide transporters in IUGR lambs. Methods On day 7 after birth, 48 newborn Hu lambs were selected from a cohort of 424 twin lambs. Normal-birth-weight and IUGR Hu lambs were allocated randomly (n = 12/group) to a control (4.09 ± 0.12 kg), IUGR (3.52 ± 0.09 kg), IUGR + 0.1% NCG (3.49 ± 0.11 kg), or IUGR + 1% Arg (3.53 ± 0.10 kg). Results At day 28, compared with the IUGR group, the IUGR groups receiving NCG and Arg had 7.4% and 7.2% greater (P < 0.05) body weight, respectively. Compared with the IUGR group, the serum concentration of insulin was greater (P < 0.05) and the cortisol was lower (P < 0.05) in the IUGR groups receiving NCG and Arg. Compared with the IUGR group, the IUGR groups receiving NCG and Arg had 13.2%–62.6% greater (P < 0.05) serum concentrations of arginine, cysteine, isoleucine, and proline. Dietary NCG or Arg to IUGR lambs resulted in greater protein abundance (P < 0.05) of peptide transporter 1 (41.9% or 38.2%) in the ileum compared with the unsupplemented IUGR lambs, respectively. Furthermore, dietary NCG or Arg treatment normalized the IUGR-induced variation (P < 0.05) in the ileal ratio of phosphorylated mTOR to total mTOR protein. Conclusion Both NCG and Arg can help mitigate the negative effect of IUGR on nutrient absorption in neonatal lambs.

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Transcriptional factor FoxM1-activated microRNA-335-3p maintains the self-renewal of neural stem cells by inhibiting p53 signaling pathway via Fmr1

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02191-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jiaoying Jia ◽

Yan Cui ◽

Zhigang Tan ◽

Min Liu ◽

Yugang Jiang

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Signaling Pathway ◽

Neurological Diseases ◽

The Self ◽

Self Renewal ◽

P53 Signaling ◽

Non Coding Rna ◽

Fetal Rats ◽

P53 Signaling Pathway

Abstract Background New mechanistic insights into the self-renewal ability and multipotent properties of neural stem cells (NSCs) are currently under active investigation for potential use in the treatment of neurological diseases. In this study, NSCs were isolated from the forebrain of fetal rats and cultured to induce NSC differentiation, which was associated with low expression of the non-coding RNA microRNA-335-3p (miR-335-3p). Methods Loss- and gain-of-function experiments were performed in NSCs after induction of differentiation. Results Overexpression of miR-335-3p or FoxM1 and inhibition of the Fmr1 or p53 signaling pathways facilitated neurosphere formation, enhanced proliferation and cell cycle entry of NSCs, but restricted NSC differentiation. Mechanistically, FoxM1 positively regulated miR-335-3p by binding to its promoter region, while miR-335-3p targeted and negatively regulated Fmr1. Additionally, the promotive effect of miR-335-3p on NSC self-renewal occurred via p53 signaling pathway inactivation. Conclusion Taken together, miR-335-3p activated by FoxM1 could suppress NSC differentiation and promote NSC self-renewal by inactivating the p53 signaling pathway via Fmr1.

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298 Antenatal Taurine Supplementation Reduces Cerebral Cell Apoptosis in Fetal Rats with Intrauterine Growth Restriction

Archives of Disease in Childhood ◽

10.1136/archdischild-2012-302724.0298 ◽

2012 ◽

Vol 97 (Suppl 2) ◽

pp. A87-A87

Author(s):

J. Liu ◽

X. Wang ◽

H. Teng ◽

N. Yang ◽

X. Ren

Keyword(s):

Cell Apoptosis ◽

Intrauterine Growth Restriction ◽

Growth Restriction ◽

Taurine Supplementation ◽

Intrauterine Growth ◽

Fetal Rats

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Ouabain rescues rat nephrogenesis during intrauterine growth restriction by regulating the complement and coagulation cascades and calcium signaling pathway

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174415007242 ◽

2015 ◽

Vol 7 (1) ◽

pp. 91-101 ◽

Cited By ~ 5

Author(s):

L. Chen ◽

J. Yue ◽

X. Han ◽

J. Li ◽

Y. Hu

Keyword(s):

Calcium Signaling ◽

Signaling Pathway ◽

Pathway Analysis ◽

Intrauterine Growth Restriction ◽

Kegg Pathway ◽

Growth Restriction ◽

Differentially Expressed ◽

Intrauterine Growth ◽

Kegg Pathway Analysis ◽

Calcium Signaling Pathway

Intrauterine growth restriction (IUGR) is associated with a reduction in the numbers of nephrons in neonates, which increases the risk of hypertension. Our previous study showed that ouabain protects the development of the embryonic kidney during IUGR. To explore this molecular mechanism, IUGR rats were induced by protein and calorie restriction throughout pregnancy, and ouabain was delivered using a mini osmotic pump. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) of the embryonic kidneys. DEGs were submitted to the Database for Annotation and Visualization and Integrated Discovery, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Maternal malnutrition significantly reduced fetal weight, but ouabain treatment had no significant effect on body weight. A total of 322 (177 upregulated and 145 downregulated) DEGs were detected between control and the IUGR group. Meanwhile, 318 DEGs were found to be differentially expressed (180 increased and 138 decreased) between the IUGR group and the ouabain-treated group. KEGG pathway analysis indicated that maternal undernutrition mainly disrupts the complement and coagulation cascades and the calcium signaling pathway, which could be protected by ouabain treatment. Taken together, these two biological pathways may play an important role in nephrogenesis, indicating potential novel therapeutic targets against the unfavorable effects of IUGR.

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Preeclampsia and intrauterine growth restriction: Role of human umbilical cord mesenchymal stem cells-trophoblast cross-talk

PLoS ONE ◽

10.1371/journal.pone.0218437 ◽

2019 ◽

Vol 14 (6) ◽

pp. e0218437 ◽

Cited By ~ 1

Author(s):

Daniela Surico ◽

Valerio Bordino ◽

Vincenzo Cantaluppi ◽

David Mary ◽

Sergio Gentilli ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Cross Talk ◽

Intrauterine Growth Restriction ◽

Growth Restriction ◽

Human Umbilical Cord ◽

Intrauterine Growth

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The Landscape of Non-Coding RNA in an Adult Pig Model of Intrauterine Growth Restriction

Cellular Physiology and Biochemistry ◽

10.1159/000494794 ◽

2018 ◽

Vol 50 (5) ◽

pp. 1764-1778 ◽

Cited By ~ 4

Author(s):

Linyuan Shen ◽

Shunhua Zhang ◽

Qiang Li ◽

Yuhua Fu ◽

Guoqing Tang ◽

...

Keyword(s):

Metabolic Syndrome ◽

Signaling Pathway ◽

Intrauterine Growth Restriction ◽

Molecular Mechanisms ◽

Target Genes ◽

Growth Restriction ◽

Differentially Expressed ◽

Quality Data ◽

Control Group ◽

Intrauterine Growth

Background/Aims: Intrauterine growth restriction (IUGR) is a risk factor for adult metabolic syndrome, but how this disease is regulated by lncRNAs and circRNAs remains elusive. Methods: Here, we employed adult IUGR and normal pigs as models to evaluate the expression of various global lncRNAs and circRNAs in pig livers using RNA-seq. Results: In total, we obtained 1,162 million raw reads of approximately 104.54 Gb high quality data. After a strict five-step filtering process, 3,368 lncRNAs were identified, including 300 differentially expressed lncRNAs (p < 0.05) in the IUGR group relative to the control group. The cis-regulatory analysis identified target genes that were enriched in specific GO terms and pathways (p < 0.05), including amino acid metabolism, oxidoreductase activity, PPAR signaling pathway, and insulin signaling pathway. These are closely related to the observed phenotypes of increased gluconeogenesis and impaired mitochondrial oxidative phosphorylation in adulthood of the IUGR group. Additionally, we also identified 403 circRNAs, of which 44 were differentially expressed (p < 0.05). Interestingly, our results identified ATF4-miR214-circRNA7964 and TCF7-miR22-3p-circRNA16347 as two competing endogenous networks, which were closely associated with the observed increase in hepatic gluconeogenesis in the IUGR group. Conclusion: Together, this study reveals a multitude of candidate lncRNAs and circRNAs involved in the development of IUGR pigs, which could facilitate further researches on the molecular mechanisms of metabolic syndrome.

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