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Local hyperthyroidism promotes pancreatic acinar cell proliferation during acute pancreatitis.
Malagola, Ermanno; Chen, Rong; Bombardo, Marta; Saponara, Enrica; Dentice, Monica; Salvatore, Domenico; Reding, Theresia; Myers, Stephen; Hills, Andrew P; Graf, Rolf; Sonda, Sabrina.
Afiliación
  • Malagola E; Swiss Hepato-Pancreato-Biliary Center, Department of Visceral and Transplantation Surgery, University Hospital, Zurich, Switzerland.
  • Chen R; Swiss Hepato-Pancreato-Biliary Center, Department of Visceral and Transplantation Surgery, University Hospital, Zurich, Switzerland.
  • Bombardo M; Swiss Hepato-Pancreato-Biliary Center, Department of Visceral and Transplantation Surgery, University Hospital, Zurich, Switzerland.
  • Saponara E; Swiss Hepato-Pancreato-Biliary Center, Department of Visceral and Transplantation Surgery, University Hospital, Zurich, Switzerland.
  • Dentice M; Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
  • Salvatore D; Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
  • Reding T; Swiss Hepato-Pancreato-Biliary Center, Department of Visceral and Transplantation Surgery, University Hospital, Zurich, Switzerland.
  • Myers S; School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Australia.
  • Hills AP; School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Australia.
  • Graf R; Swiss Hepato-Pancreato-Biliary Center, Department of Visceral and Transplantation Surgery, University Hospital, Zurich, Switzerland.
  • Sonda S; Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
J Pathol ; 248(2): 217-229, 2019 06.
Article en En | MEDLINE | ID: mdl-30714146
ABSTRACT
Proliferation of pancreatic acinar cells is a critical process in the pathophysiology of pancreatic diseases, because limited or defective proliferation is associated with organ dysfunction and patient morbidity. In this context, elucidating the signalling pathways that trigger and sustain acinar proliferation is pivotal to develop therapeutic interventions promoting the regenerative process of the organ. In this study we used genetic and pharmacological approaches to manipulate both local and systemic levels of thyroid hormones to elucidate their role in acinar proliferation following caerulein-mediated acute pancreatitis in mice. In addition, molecular mechanisms mediating the effects of thyroid hormones were identified by genetic and pharmacological inactivation of selected signalling pathways.In this study we demonstrated that levels of the thyroid hormone 3,3',5-triiodo-l-thyronine (T3) transiently increased in the pancreas during acute pancreatitis. Moreover, by using genetic and pharmacological approaches to manipulate both local and systemic levels of thyroid hormones, we showed that T3 was required to promote proliferation of pancreatic acinar cells, without affecting the extent of tissue damage or inflammatory infiltration.Finally, upon genetic and pharmacological inactivation of selected signalling pathways, we demonstrated that T3 exerted its mitogenic effect on acinar cells via a tightly controlled action on different molecular effectors, including histone deacetylase, AKT, and TGFß signalling.In conclusion, our data suggest that local availability of T3 in the pancreas is required to promote acinar cell proliferation and provide the rationale to exploit thyroid hormone signalling to enhance pancreatic regeneration. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Pancreatitis / Triyodotironina / Páncreas Exocrino / Proliferación Celular / Células Acinares / Hipertiroidismo Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Año: 2019 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Pancreatitis / Triyodotironina / Páncreas Exocrino / Proliferación Celular / Células Acinares / Hipertiroidismo Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Año: 2019 Tipo del documento: Article