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Intestinal epithelial cell proliferation is dependent on the site of massive small bowel resection

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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)/KGFR1, 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, KGFR1, 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.

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Acknowledgments

We are grateful to Dorothy Sorenson from the Microscopy and Image Analysis Laboratory of the Department of Cell and Developmental Biology, University of Michigan, for her assistance with transmission electron microscopy. This research was supported by National Institutes of Health Grant 2R01-AI044076 and 2P30 DK34933. The work was also supported in part by the University of Michigan-Comprehensive Cancer Center National Institutes of Health Grant 5 P30 CA46592, and the University of Michigan-Multipurpose Arthritic Center National Institutes of Health Grant AR20557.

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Authors and Affiliations

  1. Department of Pediatric Surgery, Medical University Graz, Graz, Austria

    Emir Q. Haxhija

  2. Section of Pediatric Surgery, Department of Surgery, University of Michigan Medical School and C. S. Mott Children’s Hospital, Mott F 3970, Box 0245, Ann Arbor, MI, 48109, USA

    Hua Yang, Ariel U. Spencer, Xiaoyi Sun & Daniel H. Teitelbaum

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  1. Emir Q. Haxhija
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  2. Hua Yang
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  3. Ariel U. Spencer
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  5. Daniel H. Teitelbaum
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Correspondence to Daniel H. Teitelbaum.

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Haxhija, E.Q., Yang, H., Spencer, A.U. et al. Intestinal epithelial cell proliferation is dependent on the site of massive small bowel resection. Pediatr Surg Int 23, 379–390 (2007). https://doi.org/10.1007/s00383-006-1855-9

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