Proteasome Inhibition of Pathologic Shedding of Enterocytes to Defend Barrier Function Requires X-Linked Inhibitor of Apoptosis Protein and Nuclear Factor κB

Foster, Derek M.; Stauffer, Stephen H.; Stone, Maria R.; Gookin, Jody L.

doi:10.1053/j.gastro.2012.03.030

Cited by 26 publications

(31 citation statements)

References 29 publications

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“…An antibody against cleaved caspase 3 identified a few cells expressing the activated protein at the villus tip within the small intestine and luminal surface in the colon. 9,28 Although this protein biomarker has been previously used for assessment of apoptosis in horses with gastrointestinal disease, 28 our study confirmed the utility of cleaved caspase 3 antibody to identify apoptotic cells in the mucosa of the small intestine and colon from horses without known intestinal abnormalities.…”

Section: Discussionsupporting

confidence: 69%

Characterization of discrete equine intestinal epithelial cell lineages

Gonzalez¹,

Kinnin²,

Blikslager³

2015

ajvr

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OBJECTIVE To characterize epithelial cells of the small intestine and colon in horses without clinical gastrointestinal abnormalities with an emphasis on the stem cell niche constituents. SAMPLE Mucosal biopsy specimens from small and large intestines obtained from 12 horses euthanized for reasons unrelated to gastrointestinal disease or systemic disease. PROCEDURES Intestinal biopsy specimens were collected by sharp dissection immediately following euthanasia. Specimens were prepared for immunohistochemical, immunofluorescence, and transmission electron microscopic imaging to detect and characterize each epithelial cell type. Antibodies against protein biomarkers for cellular identification were selected on the basis of expression in other mammalian species. RESULTS Intestinal epithelial cell types were identified by means of immunostaining and morphological characterization with transmission electron microscopy. Some differences in biomarker expression and antibody cross-reactivity were identified in equine tissue, compared with other species. However, each known type of mucosal epithelial cell was identified in equine tissue. CONCLUSIONS AND CLINICAL RELEVANCE The methodology used can enhance detection of stem cells and progenitor cells as well as postmitotic cell lineages in equine intestinal tissues. Results may have relevance to regenerative potential of intestinal mucosa and survival in horses with colic.

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Section: Discussionsupporting

confidence: 69%

Characterization of discrete equine intestinal epithelial cell lineages

Gonzalez¹,

Kinnin²,

Blikslager³

2015

ajvr

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“…Moreover, weight loss was more serious in the group that was protein deficient and infected. Compared with the neonatal mouse model and the piglet model, our young adult mouse model has the advantages of being easily executed and less expensive (28, 30). …”

Section: Discussionmentioning

confidence: 99%

“…Although whether apoptosis of intestinal epithelial cells benefits either the host or the pathogen still needs to be determined, caspase-dependent apoptosis was undoubtedly increased by C. parvum in both in vitro and in vivo models (26, 28, 30). In the present study, we showed the evidence in a murine model concerning the relationship between C.…”

Section: Discussionmentioning

confidence: 99%

Protein Malnutrition Impairs Intestinal Epithelial Cell Turnover, a Potential Mechanism of Increased Cryptosporidiosis in a Murine Model

et al. 2016

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Malnutrition and cryptosporidiosis form a vicious cycle and lead to acute and long-term growth impairment in children from developing countries. Insights into mechanisms underlying the vicious cycle will help to design rational therapies to mitigate this infection. We tested the effect of short-term protein malnutrition on Cryptosporidium parvum infection in a murine model by examining stool shedding, tissue burden, and histologic change and explored the mechanism underlying the interaction between malnutrition and cryptosporidiosis through immunostaining and immunoblotting. Protein malnutrition increased stool shedding and the number of intestine-associated C. parvum organisms, accompanied by significant suppression of C. parvum-induced caspase 3 activity and expression of PCNA and Ki67, but activation of the Akt survival pathway in intestinal epithelial cells. We find that even very brief periods of protein malnutrition may enhance (or intensify) cryptosporidiosis by suppressing C. parvum-induced cell turnover and caspase-dependent apoptosis of intestinal epithelial cells. This implicates a potential strategy to attenuate C. parvum's effects by modulating apoptosis and promoting regeneration in the intestinal epithelium.

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“…Until recently, a large animal model to study intestinal stem cell biology remained elusive. Currently, the cross reactivity of commercially available antibodies to identify specific cell types in pig intestinal tissue has been demonstrated (14, 55, 59, 68, 174, 191). Validation of tools for histologic, protein and mRNA based analysis of porcine IESCs have also been completed (68).…”

Section: Future Promise For Translational Researchmentioning

confidence: 99%

“…Additionally, pharmaceutical bioavailability and nutrient digestibility in pigs closely resemble that of humans (19, 25, 43). These characteristics have led to the use of pigs for the development of pig models of a number of gastrointestinal diseases including necrotizing enterocolitis (16, 44–48), acute mesenteric ischemia (18, 49–52), short bowel syndrome (43, 53–57), AIDS-associated Cryptosporidium infection (17, 58, 59), stress-induced intestinal dysfunction (60–63), cystic fibrosis (64, 65) and familial adenomatous polyposis (14). This review will highlight strengths and limitations of pig models of intestinal ischemia/reperfusion injury, stress-induced intestinal dysfunction and short bowel syndrome.…”

Section: Introductionmentioning

confidence: 99%

Porcine models of digestive disease: the future of large animal translational research

Gonzalez

Moeser

Blikslager

2015

Translational Research

183

167

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There is increasing interest in non-rodent translational models for the study of human disease. The pig, in particular, serves as a useful animal model for the study of pathophysiological conditions relevant to the human intestine. This review assesses currently used porcine models of gastrointestinal physiology and disease and provides a rationale for the use of these models for future translational studies. The pig has proven its utility for the study of fundamental disease conditions such as ischemia/ reperfusion injury, stress-induced intestinal dysfunction, and short bowel syndrome. Pigs have also shown great promise for the study of intestinal barrier function, surgical tissue manipulation and intervention, as well as biomaterial implantation and tissue transplantation. Advantages of pig models highlighted by these studies include the physiological similarity to human intestine as well as to mechanisms of human disease. Emerging future directions for porcine models of human disease include the fields of transgenics and stem cell biology, with exciting implications for regenerative medicine.

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Proteasome Inhibition of Pathologic Shedding of Enterocytes to Defend Barrier Function Requires X-Linked Inhibitor of Apoptosis Protein and Nuclear Factor κB

Cited by 26 publications

References 29 publications

Characterization of discrete equine intestinal epithelial cell lineages

Characterization of discrete equine intestinal epithelial cell lineages

Protein Malnutrition Impairs Intestinal Epithelial Cell Turnover, a Potential Mechanism of Increased Cryptosporidiosis in a Murine Model

Porcine models of digestive disease: the future of large animal translational research

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