Current Pediatric Reviews

Giuseppe Buonocore
Department of Molecular and Developmental Medicine
University of Siena
Siena
Italy

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The Death Pathways in the Neonatal Gut

Author(s): Michal M. Godlewski.

Abstract:

Dynamic equilibrium between apoptosis and mitosis facilitates growth and development of the intestinal mucosa in mammalian neonates. Groups of enterocytes observed dying together on the villi in the gut of the neonates suggest involvement of the paracrine factors in the propagation of the death signalling. The most potent death-inducing, paracrine factor for the enterocytes is the TGF-β. It is secreted from the macrophages and epithelial cells upon uptake of apoptotic bodies. Through its receptor complex (TGF-R I and II) and SMAD cascade it regulates the intracellular balance of the pro- and antiapoptotic proteins from the Bcl-2 family, sensitising enterocytes for other death signals (i. e. TNFα) and directing them towards apoptosis. Just before and after birth mitosis-to-apoptosis ratio shifts towards proliferation. First ingestion of colostrum, initiates the major remodelling of the gut mucosa. Apoptosis is enhanced, facilitating the removal of foetal-type enterocytes and closing of the gut barrier. Second major remodelling stage occurs after weaning, when the adaptation to the ingestion of solid foods takes place. Proliferation and cell death in the intestinal mucosa are under the direct control of a variety of growth factors (EGF, IGFs, TGF-βs) and tissue hormones (leptin, ghrelin, GLP, CCK, etc.) provided either by mothers colostrum and milk or produced in the neonate organism. Finally, uncontrolled apoptosis may lead to the weakening of the gut barrier, which results in the increased susceptibility to the intestinal disorders, pathogen infiltration and may lead to the development of the necrotising enterocolitis in the infants.

Keywords: Apoptosis, autophagy, DNA damage, neonatal development, programmed cell death, small intestine development, intestinal mucosa, Enterocytes, Anoikis, TGF-beta family

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Article Details

VOLUME: 7
ISSUE: 4
Year: 2011
Page: [337 - 345]
Pages: 9
DOI: 10.2174/157339611796892256
Price: $58