Pathological epithelial cell apoptosis and shedding in the murine small intestine

Williams, Jonathan (2013) Pathological epithelial cell apoptosis and shedding in the murine small intestine. Doctor of Philosophy thesis, University of Liverpool.

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Abstract

The intestinal epithelium represents a critical component of the gut barrier and is composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions. This epithelium prevents the entrance of harmful microorganisms, antigens and toxins from the gut lumen into the circulation. Small intestinal homeostasis is maintained by the rate of shedding of senescent enterocytes from the villus tip exactly matching the rate of generation of new cells in the crypt. However, in various localised and systemic inflammatory conditions, intestinal homeostasis may be disturbed as a result of increased IEC shedding. Such pathological IEC shedding may cause transient gaps to develop in the epithelial barrier and result in increased intestinal permeability. Although pathological IEC shedding has been implicated in the pathogenesis of inflammatory bowel disease, understanding of the underlying mechanisms remains limited. This thesis describes the development of a murine model to study this phenomenon, as IEC shedding in this species is morphologically analogous to humans. IEC shedding was induced by systemic lipopolysaccharide (LPS) administration in wild-type C57BL/6 mice, and mice deficient in TNF-receptor ... (continues)

Item Type:	Thesis (Doctor of Philosophy)
Additional Information:	Date: 2013-10 (completed)
Uncontrolled Keywords:	Lipopolysaccharide, LPS, intestinal epithelium, apoptosis, shedding, receptors tumor necrosis factor, TNF, TNFR1, TNFR2, NF-kappa B, NF-KB, NFKB, intestinal disease
Subjects:	?? RC ??
Divisions:	Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	08 Aug 2014 09:39
Last Modified:	31 Oct 2024 07:01
DOI:	10.17638/00015293
Supervisors:	Pritchard, Mark Campbell, Barry ORCID: 0000-0002-7407-012X
URI:	https://livrepository.liverpool.ac.uk/id/eprint/15293