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Wildhaber, BE; Yang, H; Haxhija, EQ; Spencer, AU; Teitelbaum, DH.
Intestinal intraepithelial lymphocyte derived angiotensin converting enzyme modulates epithelial cell apoptosis.
Apoptosis. 2005; 10(6):1305-1315
Doi: 10.1007/s10495-005-2138-y
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PubMed
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- Co-Autor*innen der Med Uni Graz
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Haxhija Emir
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- Abstract:
- BACKGROUND & AIMS: Intestinal adaptation in short bowel syndrome (SBS) consists of increased epithelial cell (EC) proliferation as well as apoptosis. Previous microarray analyses of intraepithelial lymphocytes (IEL) gene expression after SBS showed an increased expression of angiotensin converting enzyme (ACE). Because ACE has been shown to promote alveolar EC apoptosis, we examined if IEL-derived ACE plays a role in intestinal EC apoptosis. METHODS: Mice underwent either a 70% mid-intestinal resection (SBS group) or a transection (Sham group) and were studied at 7 days. ACE expression was measured, and ACE inhibition (ACE-I, enalaprilat) was used to assess ACE function. RESULTS: IEL-derived ACE was significantly elevated in SBS mice. The addition of an ACE-I to SBS mice resulted in a significant decline in EC apoptosis. To address a possible mechanism, tumor necrosis factor alpha (TNF-alpha) mRNA expression was measured. TNF-alpha was significantly increased in SBS mice, and decreased with ACE-I. Interestingly, ACE-I was not able to decrease EC apoptosis in TNF-alpha knockout mice. CONCLUSIONS: This study shows a previously undescribed expression of ACE by IEL. SBS was associated with an increase in IEL-derived ACE. ACE appears to be associated with an up-regulation of intestinal EC apoptosis. ACE-I significantly decreased EC apoptosis.
- Find related publications in this database (using NLM MeSH Indexing)
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Angiotensin-Converting Enzyme Inhibitors - administration and dosage
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Animals - administration and dosage
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Antigens, CD95 - genetics
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Apoptosis - drug effects
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Body Weight - drug effects
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Cell Proliferation - drug effects
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Cytokines - genetics
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Epithelial Cells - cytology
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Fas Ligand Protein - genetics
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Gene Expression Regulation - drug effects
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Inflammation Mediators - metabolism
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Intestinal Mucosa - drug effects
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Intestines - cytology
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Lymphocytes - cytology
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Male - cytology
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Mice - cytology
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Mice, Inbred C57BL - cytology
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Peptidyl-Dipeptidase A - genetics
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RNA, Messenger - genetics
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Short Bowel Syndrome - enzymology
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Tumor Necrosis Factor-alpha - metabolism
- Find related publications in this database (Keywords)
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angiotensin converting enzyme
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apoptosis
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epithelial cells
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intraepithelial lymphocytes
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tumor necrosis factor alpha