Tissular growth factors profile after teduglutide administration on an animal model of intestinal anastomosis

• Autor(a) principal: Costa, Beatriz P.
• Data de Publicação: 2018
• Outros Autores: Gonçalves, Ana C., Abrantes, Ana M., Alves, Raquel, Matafome, Paulo N., Seiça, Raquel, Ribeiro, Ana B. Sarmento, Botelho, M. Filomena, Castro-Sousa, Francisco
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10316/108205; https://doi.org/10.20960/nh.1326
• topic: Teduglutide; Growth factors; Intestinal anastomosis; Vascular endothelial growth factor; Connective tissue growth factor; Teduglutida; Factores de crecimiento; Anastomosis intestinal; Factor de crecimiento vascular endotelial; Factor de crecimiento del tejido conectivo; Animals; Gastrointestinal Agents; Gene Expression Regulation; Ileum; Intercellular Signaling Peptides and Proteins; Intestines; Male; Peptides; Rats; Rats, Wistar; Short Bowel Syndrome; Anastomosis, Surgical

Background: Teduglutide is an enterotrophic analogue of glucagon-like peptide-2, with an indirect and poorly understood mechanism of action, approved for the rehabilitation of short-bowel syndrome. This study aims to analyze the response of tissue growth factors to surgical injury and teduglutide administration on an animal model of intestinal anastomosis. Methods: Wistar rats (n = 59) were distributed into four groups: “ileal resection” or “laparotomy”, each one subdivided into “postoperative teduglutide administration” or “no treatment”; and sacrificed at the third or the seventh day, with ileal sample harvesting. Gene expression of insulin-like growth factor 1 (Igf1), vascular endothelial growth factor a (Vegfa), transforming growth factor β1 (Tgfβ1), connective tissue growth factor (Ctgf), fibroblast growth factor 2 (Fgf2), fibroblast growth factor 7 (Fgf7), epidermal growth factor (Egf), heparin-binding epidermal-like growth factor (Hbegf), platelet-derived growth factor b (Pdgfb) and glucagon-like peptide 2 receptor (Glp2r) was studied by real-time polymerase chain reaction. Results: Upregulation of Fgf7, Fgf2, Egf, Vegfa and Glp2r at the third day and of Pdgf at the seventh day was verified in the perianastomotic segment. Teduglutide administration was associated with higher fold-change of relative gene expression of Vegfa (3.6 ± 1.3 vs. 1.9 ± 2.0, p = 0.0001), Hbegf (2.2 ± 2.3 vs. 1.1 ± 0.9, p = 0.001), Igf1 (1.6 ± 7.6 vs. 0.9 ± 0.7, p = 0.002) and Ctgf (1.1 ± 2.1 vs. 0.6 ± 2.0, p = 0.013); and lower fold-change of Tgfβ1, Fgf7 and Glp2r. Conclusions: Those results underscore the recognized role of Igf1 and Hbegf as molecular mediators of the effects of teduglutide and suggest that other humoral factors, like Vegf and Ctgf, may also be relevant in the perioperative context. Induction of Vegfa, Igf1 and Ctgf gene expressions might indicate a favorable influence of teduglutide on the intestinal anastomotic healing.