BRD4 Inhibition Protects Against Acute Pancreatitis Through Restoring Impaired Autophagic Flux.

ABSTRACT: Impaired autophagy has been shown to play a critical role in experimental and human acute pancreatitis (AP). However, the mechanism for transcriptional regulation of autophagy remains largely unknown. In this study, we aim to explore the role of BRD4 (bromodomain-containing protein 4), a transcriptional repressor of autophagy, during AP. Changes in pancreatic BRD4 expression and the effect of BRD4 inhibition were measured in mice with AP (induced by caerulein and ethanol and palmitoleic acid) and in isolated pancreatic acinar cells stimulated with cholecystokinin (CCK). Pancreatitis severity was evaluated by serum amylase and pancreatic histopathology. The autophagic flux, the fusion of autophagosome and lysosome, and lysosomal degradation were evaluated. Sirtuin 1 (SIRT1) expression and t

SUBMITTER: Shen S 

PROVIDER: S-EPMC7227015 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature