Time-resolved Quantitative Proteome Analysis of In Vivo Intestinal Development

Hansson, Jenny; Panchaud, Alexandre; Favre, Laurent; Bosco, Nabil; Mansourian, Robert; Benyacoub, Jalil; Blum, Stéphanie; Jensen, Ole N.; Kussmann, Martin

doi:10.1074/mcp.m110.005231

Cited by 28 publications

(23 citation statements)

References 43 publications

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“…6C). Upregulation of other maturation markers in ΔIEC UN , including the duodenal-specific Akp3 gene and jejunal-specific Krt20 gene (38)(39)(40)(41), further supports the occurrence of cell maturation in the absence of NCoR1 (Fig. 6C).…”

Section: Developmental Stage-dependent Derepression Of Ugt1a1 Expressionmentioning

confidence: 76%

Intestinal NCoR1, a regulator of epithelial cell maturation, controls neonatal hyperbilirubinemia

Chen

Lü

Yueh

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Severe neonatal hyperbilirubinemia (SNH) and the onset of bilirubin encephalopathy and kernicterus result in part from delayed expression of UDP-glucuronosyltransferase 1A1 (UGT1A1) and the inability to metabolize bilirubin. Although there is a good understanding of the early events after birth that lead to the rapid increase in serum bilirubin, the events that control delayed expression of UGT1A1 during development remain a mystery. HumanizedUGT1(hUGT1) mice develop SNH spontaneously, which is linked to repression of both liver and intestinal UGT1A1. In this study, we report that deletion of intestinal nuclear receptor corepressor 1 (NCoR1) completely diminishes hyperbilirubinemia inhUGT1neonates because of intestinalUGT1A1gene derepression. Transcriptomic studies and immunohistochemistry analysis demonstrate that NCoR1 plays a major role in repressing developmental maturation of the intestines. Derepression is marked by accelerated metabolic and oxidative phosphorylation, drug metabolism, fatty acid metabolism, and intestinal maturation, events that are controlled predominantly by H3K27 acetylation. The control of NCoR1 function and derepression is linked to IKKβ function, as validated inhUGT1mice with targeted deletion of intestinal IKKβ. Physiological events during neonatal development that target activation of an IKKβ/NCoR1 loop in intestinal epithelial cells lead to derepression of genes involved in intestinal maturation and bilirubin detoxification. These findings provide a mechanism of NCoR1 in intestinal homeostasis during development and provide a key link to those events that control developmental repression of UGT1A1 and hyperbilirubinemia.

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Section: Developmental Stage-dependent Derepression Of Ugt1a1 Expressionmentioning

confidence: 76%

Intestinal NCoR1, a regulator of epithelial cell maturation, controls neonatal hyperbilirubinemia

Chen

Lü

Yueh

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…1B); pups began to acquire resistance from day 3 and were completely resistant by day 9. Reductions in susceptibility to infection following colonization will be accompanied by structural, physiological, and microbiological changes of GI tract tissues (29,30), and we therefore undertook parallel histological and immunohistochemical investigations of GI tissue in order to ensure that processes that affect susceptibility to infection can be correlated with the dynamic process of postnatal development of the rat intestine. Over the P2-to-P9 period, the length of the digestive system (stomach to colon) increased in an incremental fashion from a mean of 25.6 cm at P2 to 47.6 cm at P9 and was characterized by rapid postnatal physi- ological and anatomical development due to expansion of the small intestine and increased differentiation of the cecum (Fig.…”

Section: Resultsmentioning

confidence: 99%

Altered Innate Defenses in the Neonatal Gastrointestinal Tract in Response to Colonization by Neuropathogenic Escherichia coli

et al. 2013

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d Two-day-old (P2), but not 9-day-old (P9), rat pups are susceptible to systemic infection following gastrointestinal colonization by Escherichia coli K1. Age dependency reflects the capacity of colonizing K1 to translocate from gastrointestinal (GI) tract to blood. A complex GI microbiota developed by P2, showed little variation over P2 to P9, and did not prevent stable K1 colonization. Substantial developmental expression was observed over P2 to P9, including upregulation of genes encoding components of the small intestinal (␣-defensins Defa24 and Defa-rs1) and colonic (trefoil factor Tff2) mucus barrier. K1 colonization modulated expression of these peptides: developmental expression of Tff2 was dysregulated in P2 tissues and was accompanied by a decrease in mucin Muc2. Conversely, ␣-defensin genes were upregulated in P9 tissues. We propose that incomplete development of the mucus barrier during early neonatal life and the capacity of colonizing K1 to interfere with mucus barrier maturation provide opportunities for neuropathogen translocation into the bloodstream. The newborn infant is particularly vulnerable to systemic bacterial infection during the first 4 weeks of life, and mortality and morbidity associated with neonatal bacterial meningitis (NBM) and accompanying sepsis remain significant despite advances in antibacterial chemotherapy and supportive care (1, 2). In the developed world, Escherichia coli and group B streptococci are responsible for the majority of cases of NBM, and bacteria isolated from the cerebrospinal fluid of infected neonates invariably elaborate a protective polysaccharide capsule. Of neuroinvasive E. coli isolates, 80 to 85% express the K1 capsule (3, 4), a homopolymer of ␣-2,8-linked polysialic acid (polySia) that mimics the molecular structure of the polySia modulator of neuronal plasticity in mammalian hosts (5) and enables these strains to evade detection by a neonatal innate immune system undergoing a process of age-dependent maturation (6).Risk factors for NBM include obstetric and perinatal complications, premature birth, and low birth weight, particularly in low socioeconomic groups (7), but predisposition to infection is critically dependent on vertical transmission of the causative agent from mother to infant at or soon after birth (8). Although many aspects of the pathogenesis of E. coli K1 in NBM are unclear, maternally derived E. coli K1 bacteria are known to colonize the neonatal gastrointestinal (GI) tract (8, 9, 10), which is sterile at birth but rapidly acquires a complex microbiota that eventually converges toward a profile characteristic of the adult GI tract (11). E. coli K1 bacteria then translocate from the lumen of the small intestine or colon into the systemic circulation before entering the central nervous system (CNS) across the blood-brain barrier at the cerebral microvascular endothelium of the arachnoid membrane (12) or the blood-cerebrospinal fluid (CSF) barrier at the choroid plexus epithelium (13).Many of the temporal and spatial aspects of NBM can...

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“…The mucosal development is dominated by the proliferation and differentiation of epithelial cells14. However, studies designed to study the proliferation and differentiation processes of intestinal epithelial cells have been largely conducted using cell culture models, and this area of intestinal mucosal renewal remains poorly understood15.…”

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confidence: 99%

Energy metabolism in intestinal epithelial cells during maturation along the crypt-villus axis

Yang

Wang

Xiong

et al. 2016

Sci Rep

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Intestinal epithelial cells continuously migrate and mature along crypt-villus axis (CVA), while the changes in energy metabolism during maturation are unclear in neonates. The present study was conducted to test the hypothesis that the energy metabolism in intestinal epithelial cells would be changed during maturation along CVA in neonates. Eight 21-day-old suckling piglets were used. Intestinal epithelial cells were isolated sequentially along CVA, and proteomics was used to analyze the changes in proteins expression in epithelial cells along CVA. The identified differentially expressed proteins were mainly involved in cellular process, metabolic process, biological regulation, pigmentation, multicellular organizational process and so on. The energy metabolism in intestinal epithelial cells of piglets was increased from the bottom of crypt to the top of villi. Moreover, the expression of proteins related to the metabolism of glucose, most of amino acids, and fatty acids was increased in intestinal epithelial cells during maturation along CVA, while the expression of proteins related to glutamine metabolism was decreased from crypt to villus tip. The expression of proteins involved in citrate cycle was also increased intestinal epithelial cells during maturation along CVA. Moreover, dietary supplementation with different energy sources had different effects on intestinal structure of weaned piglets.

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Time-resolved Quantitative Proteome Analysis of In Vivo Intestinal Development

Cited by 28 publications

References 43 publications

Intestinal NCoR1, a regulator of epithelial cell maturation, controls neonatal hyperbilirubinemia

Intestinal NCoR1, a regulator of epithelial cell maturation, controls neonatal hyperbilirubinemia

Altered Innate Defenses in the Neonatal Gastrointestinal Tract in Response to Colonization by Neuropathogenic Escherichia coli

Energy metabolism in intestinal epithelial cells during maturation along the crypt-villus axis

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