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Local hyperthyroidism promotes pancreatic acinar cell proliferation during acute pancreatitis

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journal contribution
posted on 2023-05-20, 01:23 authored by Malagola, E, Chen, R, Bombardo, M, Saponara, E, Dentice, M, Salvatore, D, Reding, T, Stephen MyersStephen Myers, Andrew HillsAndrew Hills, Graf, R, Sabrina SondaSabrina Sonda
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. Inthis context, elucidating the signalling pathways that trigger and sustain acinar proliferation is pivotal todevelop therapeutic interventions promoting the regenerative process of the organ.In this study we usedgenetic and pharmacological approaches to manipulate both local and systemic levels of thyroid hormones toelucidate 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 pharmacologicalinactivation of selected signalling pathways. In this study we demonstrated that levels of the thyroid hormone3,3′,5-triiodo-L-thyronine (T3) transiently increased in the pancreas during acute pancreatitis. Moreover, by usinggenetic and pharmacological approaches to manipulate both local and systemic levels of thyroid hormones, weshowed that T3 was required to promote proliferation of pancreatic acinar cells, without affecting the extentof tissue damage or inflammatory infiltration.Finally, upon genetic and pharmacological inactivation of selectedsignalling pathways, we demonstrated that T3 exerted its mitogenic effect on acinar cells via a tightly controlledaction on different molecular effectors, including histone deacetylase, AKT, and TGFsignalling.In conclusion, ourdata suggest that local availability of T3 in the pancreas is required to promote acinar cell proliferation and providethe rationale to exploit thyroid hormone signalling to enhance pancreatic regeneration.


Publication title

Journal of Pathology








School of Health Sciences


John Wiley & Sons Ltd

Place of publication

The Atrium, Southern Gate, Chichester, England, W Sussex, Po19 8Sq

Rights statement

Copyright 2019 Pathological Society of Great Britain and Ireland

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  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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