Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Haxhija, EQ; Yang, H; Spencer, AU; Sun, X; Teitelbaum, DH.
Intestinal epithelial cell proliferation is dependent on the site of massive small bowel resection.
Pediatr Surg Int. 2007; 23(5): 379-390.
Doi: 10.1007/s00383-006-1855-9
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PubMed
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- Haxhija Emir
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- Abstract:
- Early intestinal adaptation after massive small bowel resection (SBR) is driven by increased epithelial cell (EC) proliferation. There is a clear clinical difference in the post-operative course of patients after the loss of proximal (P) compared to distal (D) small bowel. This study examined the effects of the site of SBR on post-resectional intestinal adaptation, and investigated the potential mechanisms involved. C57BL/6J mice (n = 7/group) underwent: (1) 60% P-SBR, (2) 60% D-SBR, (3) 60% mid (M)-SBR and (4) SHAM-operation (transection/reanastomosis). Mice were sacrificed at 7 days after surgery and ECs and adjacent mucosal lymphocytes (IELs) isolated. Adaptation was assessed in both jejunum and ileum by quantification of villus height, crypt depth, villus cell size, crypt cell size (microns), goblet cell number, and EC proliferation (%BrdU incorporation). Proliferation signalling pathways including keratinocyte growth factor (KGF)/KGFR(1), IL-7/IL-7R, and epidermal growth factor receptor (EGFR) were measured by RT-PCR. Expression of IL-7 was further analysed by immunofluorescence. Data were analyzed using ANOVA. All three SBR models led to significant increases in villus height, crypt depth, goblet cell numbers and EC proliferation rate when compared to respective SHAM groups. The strongest morphometric changes were found for jejunal segments after M-SBR and for ileal segments after P-SBR. Furthermore, morphometric analysis showed that at 1-week post-resection a tremendous increase in EC numbers occurred in jejunal villi (cell hyperplasia), whereas a significant increase in EC size predominated in ileal villi (cell hypertrophy). mRNA expression of KGF, KGFR(1), IL-7R, and EGFR showed a significant increase only after D-SBR, whereas IL-7 increased significantly after SBR in all investigated models, and this was confirmed by immunofluorescence studies. Early intestinal adaptation shows distinct differences depending on the site of SBR, and is predominately driven by cell hyperplasia in jejunal villi and cell hypertrophy in ileal villi. However, the exact mechanisms, which guide these signalling pathways are still unclear.
- Find related publications in this database (using NLM MeSH Indexing)
- Adaptation, Physiological - physiology
- Animals - physiology
- Cell Proliferation - physiology
- Cell Size - physiology
- Epithelial Cells - physiology
- Fluorescent Antibody Technique - methods
- Intercellular Signaling Peptides and Proteins - metabolism
- Interleukin-7 - metabolism
- Intestine, Small - physiology
- Lymphocytes - physiology
- Male - physiology
- Mice - physiology
- Mice, Inbred C57BL - physiology
- Postoperative Period - physiology
- Receptors, Growth Factor - metabolism
- Receptors, Interleukin-7 - metabolism
- Recovery of Function - metabolism
- Reverse Transcriptase Polymerase Chain Reaction - methods
- Signal Transduction - physiology
- Specific Pathogen-Free Organisms - physiology
- Find related publications in this database (Keywords)
- short bowel syndrome
- proliferation
- IL-7
- keratinocyte growth factor
- epidermal growth factor receptor