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Erschienen in: Pediatric Surgery International 1/2023

01.12.2023 | Original Article

The effect of hepatocyte growth factor on intestinal adaption in an experimental model of short bowel syndrome

verfasst von: George Bagias, Evangelos P. Misiakos, Anestis Charalampopoulos, Nick Zavras, Stratigoula Sakellariou, Dimitrios Schizas, Igor Sukhotnik, Evangelos Giamarelos, Emmanouil Pikoulis

Erschienen in: Pediatric Surgery International | Ausgabe 1/2023

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Abstract

Purpose

Nowadays, the standard therapy for patients with short bowel syndrome is parenteral nutrition (PN). Various growth factors have been tested to achieve weaning from prolonged PN administration. We evaluated the effect of hepatocyte growth factor (HGF) on structural intestinal adaptation and cell proliferation in a rat model of SBS.

Methods

Thirty Sprague–Dawley rats were divided into three groups; group A rats (sham) underwent bowel transection, group B rats underwent a 75% bowel resection, and group C rats underwent the same procedure but were treated postoperatively with HGF. Histopathologic parameters of intestinal adaptation were determined, while microarray and rt-PCR analyses of ileal RNA were also performed.

Results

Treatment with HGF resulted in significant increase in body weight, while the jejunal and ileal villus height and crypt depth were increased in HGF rats (36%, p < 0.05 and 27%, p < 0.05 respectively). Enterocyte proliferation was also significantly increased in HGF rats (21% p < 0.05). Microarray and quantitative rt-PCR analyses showed that the genes hgfac, rac 1, cdc42, and akt 1 were more than twofold up-regulated after HGF treatment.

Conclusion

HGF emerges as a growth factor that enhances intestinal adaptation. The future use of HGF may potentially reduce the requirement for PN in SBS patients.
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Literatur
14.
Zurück zum Zitat Misiakos EP, Agrogiannis G, Patapis P, Dontas I, Petropoulos K, Machairas N, Giamarellos-Bourboulis E, Liakakos T, Machairas A (2013) Expression of tissue IGF 1, TGFbeta and EGFR in the sequential steps of intestinal adaptation in a rat model of short bowel syndrome. Acta Chir Belg 113:129–138CrossRefPubMed Misiakos EP, Agrogiannis G, Patapis P, Dontas I, Petropoulos K, Machairas N, Giamarellos-Bourboulis E, Liakakos T, Machairas A (2013) Expression of tissue IGF 1, TGFbeta and EGFR in the sequential steps of intestinal adaptation in a rat model of short bowel syndrome. Acta Chir Belg 113:129–138CrossRefPubMed
17.
Zurück zum Zitat Nakamura T, Nawa K, Ichihara A (1984) Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats. Biochem Biophys Res Commun 122:1450–1459CrossRefPubMed Nakamura T, Nawa K, Ichihara A (1984) Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats. Biochem Biophys Res Commun 122:1450–1459CrossRefPubMed
18.
Zurück zum Zitat Russell WE, McGowan JA, Bucher NL (1984) Partial characterization of a hepatocyte growth factor from rat platelets. J Cell Physiol 119:183–192CrossRefPubMed Russell WE, McGowan JA, Bucher NL (1984) Partial characterization of a hepatocyte growth factor from rat platelets. J Cell Physiol 119:183–192CrossRefPubMed
19.
Zurück zum Zitat Miyazawa K, Tsubouchi H, Naka D et al (1989) Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor. Biochem Biophys Res Commun 163:967–973CrossRefPubMed Miyazawa K, Tsubouchi H, Naka D et al (1989) Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor. Biochem Biophys Res Commun 163:967–973CrossRefPubMed
21.
Zurück zum Zitat Nakamura T, Nishizawa T, Hagiya M et al (1989) Molecular cloning and expression of human hepatocyte growth factor. Nature 342:440–443CrossRefPubMed Nakamura T, Nishizawa T, Hagiya M et al (1989) Molecular cloning and expression of human hepatocyte growth factor. Nature 342:440–443CrossRefPubMed
23.
Zurück zum Zitat Misiakos EP, Kato T, Levi D, et al (2000) Pediatric small bowel transplantation. In: Tejani A, Harmon WE, Fine R, eds. Pediatric Solid Organ Transplantation. Munksgaard, Misiakos EP, Kato T, Levi D, et al (2000) Pediatric small bowel transplantation. In: Tejani A, Harmon WE, Fine R, eds. Pediatric Solid Organ Transplantation. Munksgaard,
24.
Zurück zum Zitat Levin MS, Rubin DC (2008) Intestinal adaptation. The biology of the intestinal response to resection and disease. In: A. Intestinal failure. Diagnosis, management and transplantation. Blackwell Publishing, Inc., Malden MA, pp. 45–54. Levin MS, Rubin DC (2008) Intestinal adaptation. The biology of the intestinal response to resection and disease. In: A. Intestinal failure. Diagnosis, management and transplantation. Blackwell Publishing, Inc., Malden MA, pp. 45–54.
25.
Zurück zum Zitat Wilson TJ, Ponder BA, Wright NA (1985) Use of a mouse chimaeric model to study cell migration patterns in the small intestinal epithelium. Cell Tissue Kinet 18:333–344PubMed Wilson TJ, Ponder BA, Wright NA (1985) Use of a mouse chimaeric model to study cell migration patterns in the small intestinal epithelium. Cell Tissue Kinet 18:333–344PubMed
26.
Zurück zum Zitat Pinto D, Clevers H (2005) Wnt control of stem cells and differentiation in the intestinal epithelium. Exp Cell Res 306:357–363CrossRefPubMed Pinto D, Clevers H (2005) Wnt control of stem cells and differentiation in the intestinal epithelium. Exp Cell Res 306:357–363CrossRefPubMed
32.
Zurück zum Zitat Williamson RC, Buchholtz TW, Malt RA (1978) Humoral stimulation of cell proliferation in small bowel after transection and resection in rats. Gastroenterology 75:249–254CrossRefPubMed Williamson RC, Buchholtz TW, Malt RA (1978) Humoral stimulation of cell proliferation in small bowel after transection and resection in rats. Gastroenterology 75:249–254CrossRefPubMed
33.
Zurück zum Zitat Dekaney CM, Fong JJ, Rigby RJ, Lund PK, Henning SJ, Helmrath MA (2007) Expansion of intestinal stem cells associated with long-term adaptation following ileocecal resection in mice. American Journal of Physiology-Gastrointestinal and Liver Physiology 293:G1013-G1022. doi: https://doi.org/10.1152/ajpgi.00218.2007. Dekaney CM, Fong JJ, Rigby RJ, Lund PK, Henning SJ, Helmrath MA (2007) Expansion of intestinal stem cells associated with long-term adaptation following ileocecal resection in mice. American Journal of Physiology-Gastrointestinal and Liver Physiology 293:G1013-G1022. doi: https://​doi.​org/​10.​1152/​ajpgi.​00218.​2007.
39.
Zurück zum Zitat Bierne H, Cossart P (2002) InlB, a surface protein of Listeria monocytogenes that behaves as an invasin and a growth factor. J Cell Sci 115:3357–3367CrossRefPubMed Bierne H, Cossart P (2002) InlB, a surface protein of Listeria monocytogenes that behaves as an invasin and a growth factor. J Cell Sci 115:3357–3367CrossRefPubMed
41.
Zurück zum Zitat Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB (1999) NFkappaB activation by tumour necrosis factor requires the Akt serine–threonine kinase. Nature 401:82–85CrossRefPubMed Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB (1999) NFkappaB activation by tumour necrosis factor requires the Akt serine–threonine kinase. Nature 401:82–85CrossRefPubMed
46.
Zurück zum Zitat Ogura Y, Hamanoue M, Tanabe G et al (2001) Hepatocyte growth factor promotes liver regeneration and protein synthesis after hepatectomy in cirrhotic rats. Hepatogastroenterology 48:545–549PubMed Ogura Y, Hamanoue M, Tanabe G et al (2001) Hepatocyte growth factor promotes liver regeneration and protein synthesis after hepatectomy in cirrhotic rats. Hepatogastroenterology 48:545–549PubMed
50.
Zurück zum Zitat Ido A, Moriuchi A, Numata M, Murayama T, Teramukai S, Marusawa H, Yamaji N, Setoyama H, Kim ID, Chiba T, Higuchi S, Yokode M, Fukushima M, Shimizu A, Ido TH, A., Moriuchi, A., Numata, M., Murayama, T., Teramukai, S., Marusawa, H., Yamaji, N., Setoyama, H., Kim, I. D., Chiba, T., Higuchi, S., Yokode, M., Fukushima, M., Shimizu, A., & Tsubouchi, H. (2011) Safety and pharmacokinetics of recombinant human hepatocyte growth factor (rh-HGF) in patients with fulminant hepatitis: a phase I/II clinical trial, following preclinical studies to ensure safety. J Transl Med 9:55. https://doi.org/10.1186/1479-5876-9-55CrossRefPubMedPubMedCentral Ido A, Moriuchi A, Numata M, Murayama T, Teramukai S, Marusawa H, Yamaji N, Setoyama H, Kim ID, Chiba T, Higuchi S, Yokode M, Fukushima M, Shimizu A, Ido TH, A., Moriuchi, A., Numata, M., Murayama, T., Teramukai, S., Marusawa, H., Yamaji, N., Setoyama, H., Kim, I. D., Chiba, T., Higuchi, S., Yokode, M., Fukushima, M., Shimizu, A., & Tsubouchi, H. (2011) Safety and pharmacokinetics of recombinant human hepatocyte growth factor (rh-HGF) in patients with fulminant hepatitis: a phase I/II clinical trial, following preclinical studies to ensure safety. J Transl Med 9:55. https://​doi.​org/​10.​1186/​1479-5876-9-55CrossRefPubMedPubMedCentral
Metadaten
Titel
The effect of hepatocyte growth factor on intestinal adaption in an experimental model of short bowel syndrome
verfasst von
George Bagias
Evangelos P. Misiakos
Anestis Charalampopoulos
Nick Zavras
Stratigoula Sakellariou
Dimitrios Schizas
Igor Sukhotnik
Evangelos Giamarelos
Emmanouil Pikoulis
Publikationsdatum
01.12.2023
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Surgery International / Ausgabe 1/2023
Print ISSN: 0179-0358
Elektronische ISSN: 1437-9813
DOI
https://doi.org/10.1007/s00383-022-05341-6

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