Bombesin-induced pancreatic regeneration in pigs is mediated by p46(Shc)/p52(Shc) and p42/p44 mitogen-activated protein kinase upregulation

Stefano Fiorucci, A. Bufalari, E. Distrutti, A. Bufalari, L. Lanfrancone, A. Servoli, L. Sarpi, B. Federici, A. Bartoli, A. Morelli, L. Moggi

Research output: Contribution to journalArticle

Abstract

Background: In several animal species the pancreas has the capacity to partially regenerate in a self regulating process. A complex network of growth factors modulates this process. There is evidence that bombesin stimulates pancreatic regeneration in rodents. Whether bombesin stimulates pancreas regrowth in large mammals is unknown. Shc proteins, the target of tyrosine kinase-coupled receptors, activate p42 and p44 mitogen-activated protein (MAP) kinase and induce the transcriptional upregulation of genes involved in cell proliferation. The aims of our study were to determine whether bombesin stimulates pancreatic growth in large mammals and whether this event requires Shc-MAP kinase pathway upregulation. Methods: Three groups of pigs were submitted to sham operation (group 1); to subtotal (70%) distal pancreatectomy (group 2), and to subtotal pancreatectomy followed by bombesin (5 mg three times daily) for 4 weeks (group 3). After a 4-week follow-up a second laparotomy was performed, and the residual pancreas removed. p46(Shc), p52(Shc) and p66(Shc), Grb2, and p42/p44 MAP kinase expression and phosphorylation were measured either in freshly isolated pancreatic acinar cells or whole pancreatic extracts. Results: In vivo bombesin administration resulted in: 1) ~100% growth of pancreatic duodenal lobe; 2) rapid recovery from exocrine pancreatic failure; and 3) a threefold increase in the rate of pancreatic acinar cell proliferation. Incubating freshly isolated pancreatic acinar cells with bombesin resulted in time- and concentration-dependent stimulation of p46(Shc)/p52(Shc) phosphorylation, Shc-Grb2 complex formation, and p42/p44 MAP kinase activation. In vivo bombesin administration significantly upregulated p46(Shc)/p52(Shc) and MAP kinase expression and/or activity in whole pancreatic extracts. Conclusions: In vivo chronic bombesin administration stimulates pancreatic regeneration after pancreatectomy in large mammals. Bombesin-stimulated pancreatic growth is associated with upregulation of the Shc-Grb2-SOS-Ras-MAP kinase pathway.

Original languageEnglish
Pages (from-to)1310-1320
Number of pages11
JournalScandinavian Journal of Gastroenterology
Volume33
Issue number12
DOIs
Publication statusPublished - 1998

Fingerprint

Bombesin
Mitogen-Activated Protein Kinase 1
Regeneration
Up-Regulation
Swine
Pancreatectomy
Acinar Cells
Pancreatic Extracts
Mitogen-Activated Protein Kinases
Pancreas
Mammals
Growth
Phosphorylation
Cell Proliferation
Receptor Protein-Tyrosine Kinases
Protein-Tyrosine Kinases
Laparotomy
Rodentia
Intercellular Signaling Peptides and Proteins

Keywords

  • Bombesin
  • Mammalian pancreas
  • Mitogen-activated protein kinase
  • Shc

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Bombesin-induced pancreatic regeneration in pigs is mediated by p46(Shc)/p52(Shc) and p42/p44 mitogen-activated protein kinase upregulation. / Fiorucci, Stefano; Bufalari, A.; Distrutti, E.; Bufalari, A.; Lanfrancone, L.; Servoli, A.; Sarpi, L.; Federici, B.; Bartoli, A.; Morelli, A.; Moggi, L.

In: Scandinavian Journal of Gastroenterology, Vol. 33, No. 12, 1998, p. 1310-1320.

Research output: Contribution to journalArticle

Fiorucci, S, Bufalari, A, Distrutti, E, Bufalari, A, Lanfrancone, L, Servoli, A, Sarpi, L, Federici, B, Bartoli, A, Morelli, A & Moggi, L 1998, 'Bombesin-induced pancreatic regeneration in pigs is mediated by p46(Shc)/p52(Shc) and p42/p44 mitogen-activated protein kinase upregulation', Scandinavian Journal of Gastroenterology, vol. 33, no. 12, pp. 1310-1320. https://doi.org/10.1080/00365529850172412
Fiorucci, Stefano ; Bufalari, A. ; Distrutti, E. ; Bufalari, A. ; Lanfrancone, L. ; Servoli, A. ; Sarpi, L. ; Federici, B. ; Bartoli, A. ; Morelli, A. ; Moggi, L. / Bombesin-induced pancreatic regeneration in pigs is mediated by p46(Shc)/p52(Shc) and p42/p44 mitogen-activated protein kinase upregulation. In: Scandinavian Journal of Gastroenterology. 1998 ; Vol. 33, No. 12. pp. 1310-1320.
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title = "Bombesin-induced pancreatic regeneration in pigs is mediated by p46(Shc)/p52(Shc) and p42/p44 mitogen-activated protein kinase upregulation",
abstract = "Background: In several animal species the pancreas has the capacity to partially regenerate in a self regulating process. A complex network of growth factors modulates this process. There is evidence that bombesin stimulates pancreatic regeneration in rodents. Whether bombesin stimulates pancreas regrowth in large mammals is unknown. Shc proteins, the target of tyrosine kinase-coupled receptors, activate p42 and p44 mitogen-activated protein (MAP) kinase and induce the transcriptional upregulation of genes involved in cell proliferation. The aims of our study were to determine whether bombesin stimulates pancreatic growth in large mammals and whether this event requires Shc-MAP kinase pathway upregulation. Methods: Three groups of pigs were submitted to sham operation (group 1); to subtotal (70{\%}) distal pancreatectomy (group 2), and to subtotal pancreatectomy followed by bombesin (5 mg three times daily) for 4 weeks (group 3). After a 4-week follow-up a second laparotomy was performed, and the residual pancreas removed. p46(Shc), p52(Shc) and p66(Shc), Grb2, and p42/p44 MAP kinase expression and phosphorylation were measured either in freshly isolated pancreatic acinar cells or whole pancreatic extracts. Results: In vivo bombesin administration resulted in: 1) ~100{\%} growth of pancreatic duodenal lobe; 2) rapid recovery from exocrine pancreatic failure; and 3) a threefold increase in the rate of pancreatic acinar cell proliferation. Incubating freshly isolated pancreatic acinar cells with bombesin resulted in time- and concentration-dependent stimulation of p46(Shc)/p52(Shc) phosphorylation, Shc-Grb2 complex formation, and p42/p44 MAP kinase activation. In vivo bombesin administration significantly upregulated p46(Shc)/p52(Shc) and MAP kinase expression and/or activity in whole pancreatic extracts. Conclusions: In vivo chronic bombesin administration stimulates pancreatic regeneration after pancreatectomy in large mammals. Bombesin-stimulated pancreatic growth is associated with upregulation of the Shc-Grb2-SOS-Ras-MAP kinase pathway.",
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T1 - Bombesin-induced pancreatic regeneration in pigs is mediated by p46(Shc)/p52(Shc) and p42/p44 mitogen-activated protein kinase upregulation

AU - Fiorucci, Stefano

AU - Bufalari, A.

AU - Distrutti, E.

AU - Bufalari, A.

AU - Lanfrancone, L.

AU - Servoli, A.

AU - Sarpi, L.

AU - Federici, B.

AU - Bartoli, A.

AU - Morelli, A.

AU - Moggi, L.

PY - 1998

Y1 - 1998

N2 - Background: In several animal species the pancreas has the capacity to partially regenerate in a self regulating process. A complex network of growth factors modulates this process. There is evidence that bombesin stimulates pancreatic regeneration in rodents. Whether bombesin stimulates pancreas regrowth in large mammals is unknown. Shc proteins, the target of tyrosine kinase-coupled receptors, activate p42 and p44 mitogen-activated protein (MAP) kinase and induce the transcriptional upregulation of genes involved in cell proliferation. The aims of our study were to determine whether bombesin stimulates pancreatic growth in large mammals and whether this event requires Shc-MAP kinase pathway upregulation. Methods: Three groups of pigs were submitted to sham operation (group 1); to subtotal (70%) distal pancreatectomy (group 2), and to subtotal pancreatectomy followed by bombesin (5 mg three times daily) for 4 weeks (group 3). After a 4-week follow-up a second laparotomy was performed, and the residual pancreas removed. p46(Shc), p52(Shc) and p66(Shc), Grb2, and p42/p44 MAP kinase expression and phosphorylation were measured either in freshly isolated pancreatic acinar cells or whole pancreatic extracts. Results: In vivo bombesin administration resulted in: 1) ~100% growth of pancreatic duodenal lobe; 2) rapid recovery from exocrine pancreatic failure; and 3) a threefold increase in the rate of pancreatic acinar cell proliferation. Incubating freshly isolated pancreatic acinar cells with bombesin resulted in time- and concentration-dependent stimulation of p46(Shc)/p52(Shc) phosphorylation, Shc-Grb2 complex formation, and p42/p44 MAP kinase activation. In vivo bombesin administration significantly upregulated p46(Shc)/p52(Shc) and MAP kinase expression and/or activity in whole pancreatic extracts. Conclusions: In vivo chronic bombesin administration stimulates pancreatic regeneration after pancreatectomy in large mammals. Bombesin-stimulated pancreatic growth is associated with upregulation of the Shc-Grb2-SOS-Ras-MAP kinase pathway.

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