Preview

PDF Bombardo41598_2...pdf | Download (14MB) | Preview

Abstract

Adult pancreatic acinar cells have the ability to re-enter the cell cycle and proliferate upon injury or tissue loss. Despite this mitotic ability, the extent of acinar proliferation is often limited and unable to completely regenerate the injured tissue or restore the initial volume of the organ, thus leading to pancreatic dysfunction. Identifying molecular determinants of enhanced proliferation is critical to overcome this issue. In this study, we discovered that Murphy Roths Large (MRL/MpJ) mice can be exploited to identify molecular effectors promoting acinar proliferation upon injury, with the ultimate goal to develop therapeutic regimens to boost pancreatic regeneration. Our results show that, upon cerulein-induced acinar injury, cell proliferation was enhanced and cell cycle components up-regulated in the pancreas of MRL/MpJ mice compared to the control strain C57BL/6. Initial damage of acinar cells was exacerbated in these mice, manifested by increased serum levels of pancreatic enzymes, intra-pancreatic trypsinogen activation and acinar cell apoptosis. In addition, MRL/MpJ pancreata presented enhanced inflammation, de-differentiation of acinar cells and acinar-to-ductal metaplasia. Manipulation of inflammatory levels and mitogenic stimulation with the thyroid hormone 5,3-L-tri-iodothyronine revealed that factors derived from initial acinar injury rather than inflammatory injury promote the replicative advantage in MRL/MpJ mice.

Item Type:	Article
Authors/Creators:	Bombardo, M and Malagola, E and Chen, R and Carta, A and Seleznik, GM and Hills, AP and Graf, R and Sonda, S
Keywords:	Pancreatitis, mouse models, organ regeneration
Journal or Publication Title:	Scientific Reports
Publisher:	Nature Publishing Group
ISSN:	2045-2322
DOI / ID Number:	https://doi.org/10.1038/s41598-018-27422-0
Copyright Information:	Copyright 2018 The AuthorsLicensed under Creative Commons Attribution 4.0 International (CC BY 4.0)https://creativecommons.org/licenses/by/4.0/
Related URLs:	Google Scholar: Hills, AP UTAS Profile: Hills, AP
Item Statistics:	View statistics for this item

Actions (login required)

Item Control Page