Abstract
Introduction
Transforming growth factor beta (TGF-β) has been shown to affect epithelial cell differentiation and proliferation through epithelial-mesenchymal and epithelial-immune cell interaction. In the present study, we evaluated the effect of TGF-β2-enriched polymeric diet (Modulen) on enterocyte turnover in a rat model of short bowel syndrome (SBS).
Methods
Male rats were divided into four groups: Sham rats and Sham-TGF-β rats underwent bowel transection, and were treated with TGF-β from the 4th postoperative day, SBS rats underwent a 75% bowel resection, and SBS-TGF-β rats underwent bowel resection and were treated with TGF-β-enriched diet similar to Group B. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined on day 15. Real-time PCR was used to determine Bax and Bcl-2 mRNA expression.
Results
Treatment of SBS animals with TGF-β2 supplemented diet led to a significant decrease (vs. SBS rats) in bowel weight in ileum (18%, P < 0.05), mucosal DNA content in jejunum (threefold decrease, P < 0.05) and ileum (2.5-fold decrease, P < 0.05), and mucosal protein in jejunum (twofold decrease, P < 0.05) compared to SBS-untreated animals (Group B). Treatment with TGF-β resulted in a mild decrease in enterocyte proliferation in jejunum (25%, P < 0.05) and ileum (18%, P < 0.05). A decreased cell apoptosis in the SBS-TGF-β group was accompanied by a decreased Bax and increased Bcl-2 mRNA expression.
Conclusions
In a rat model of SBS, dietary TGF-β inhibits intestinal adaptation. Decreased enterocyte proliferation is responsible for this effect.
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Refernces
O’Brien DP, Nelson LA, Huang FS, Warner BW (2001) Intestinal adaptation: structure, function, and regulation. Semin Pediatr Surg 10:55–64
Sigalet DL, Martin GR (1998) Mechanisms underlying intestinal adaptation after massive intestinal resection in the rats. J Pediatr Surg 33:889–892
Podolsky DK (1994) Peptide growth factors in the gastrointestinal tract. In: Johnson LR (ed) Physiology of the gastrointestinal tract, 3rd edn. Raven Press, New York, pp 129–167
Massague J (1992) Receptors for the TGF-β family. Cell 69:1067–1070
Kretzschmar M, Massague J (1998) SMADs: mediators and regulators of TGF-beta signaling. Curr Opin Genet Dev 8:103–111
Roberts AB, Sporn MB (1993) Physiological actions and clinical applications of transforming growth factor-beta (TGF-beta). Growth Factors 8:1–9
Massaguè J (1996) TGFβ signaling: receptors, transducers, and mad proteins. Cell 85:947–950
Sukhotnik I, Coran AG, Kramer A, Shiloni E, Mogilner J (2005) Advances in the research of the short bowel syndrome: an updated review. Pediatr Surg Int 21:947–953
Sukhotnik I, Shiloni E, Krausz MM, Yakirevich E, Sabo E, Mogilner J, Coran AG, Mac Harmon C (2003) Low fat diet impairs postresection intestinal adaptation in a rat model of short bowel syndromt. J Pediatr Surg 38:1182–1187
Chromozinski P (1993) A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. BioTechniques 15:532–536
Sukhotnik I, Krausz MM, Siplovich L, Shiloni E (2003) Peptide growth factors and intestinal adaptation in short bowel syndrome. Isr Med Assoc J 5:184–187
Oz HS, Ray M, Chen TS, McClain CJ (2004) Efficacy of a transforming growth factor beta 2 containing nutritional support formula in a murine model of inflammatory bowel disease. J Am Coll Nutr 23:220–226
Goumans MJ, Mummery C (2000) Functional analysis of the TGFb receptor/Smad pathway through gene ablation in mice. Int J Dev Biol 44:253–265
Massague J (1998) TGF-b signal transduction. Ann Rev Biochem 67:753–791
Mowat AM, Garside P, Fitton LA, Higley HR, Carlino JA (1996) Regulatory activity of endogenous and exogenous transforming growth factor beta in experimental intestinal immunopathology. Growth Factors 13:75–85
Stern LE, Huang F, Kemp CJ, Falcone RA Jr, Erwin CR, Warner BW (2000) Bax is required for increased enterocyte apoptosis after massive small bowel resection. Surgery 128:165–170
Vandeghoof JA (1996) Short bowel syndrome. Clin Perinatol 23:377–386
Matarese LE, Seidner DL, Steiger E (2004) Growth hormone, glutamine, and modified diet for intestinal adaptation. J Am Diet Assoc 104:1265–1272
Biasi F, Vizio B, Mascia C, Gaia E, Zarkovic N, Chiarpotto E, Leonarduzzi G, Poli G (2006) c-Jun N-terminal kinase upregulation as a key event in the proapoptotic interaction between transforming growth factor-beta1 and 4-hydroxynonenal in colon mucosa. Free Radic Biol Med 41:443–454
Acknowledgments
This work was supported by an Israel Science Foundation (ISF) research grant (No 1135/08).
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I. Sukhotnik and J.G. Mogilner equally contributed to preparation of the manuscript.
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Sukhotnik, I., Mogilner, J.G., Ben Lulu, S. et al. Nutritional supplementation with transforming growth factor-beta inhibits intestinal adaptation after massive small bowel resection in a rat. Pediatr Surg Int 27, 211–216 (2011). https://doi.org/10.1007/s00383-010-2774-3
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DOI: https://doi.org/10.1007/s00383-010-2774-3