Critical Role of TFEB-Mediated Lysosomal Biogenesis in Alcohol-Induced Pancreatitis in Mice and Humans.

ABSTRACT:

Background & aims

Alcohol abuse is the major cause of experimental and human pancreatitis but the molecular mechanisms remain largely unknown. We investigated the role of transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, in the pathogenesis of alcoholic pancreatitis.

Methods

Using a chronic plus acute alcohol binge (referred to as Gao-binge) mouse model, we analyzed pancreas injury, autophagic flux, zymogen granule removal, TFEB nuclear translocation and lysosomal biogenesis in GFP-LC3 transgenic mice, acinar cell-specific Atg5 knockout (KO) and TFEB KO mice as well as their matched wild type mice.

Results

We found that Gao-binge alcohol induced typical features of pancreatitis in mice with increased serum amylase and lipase activities, pancr

SUBMITTER: Wang S 

PROVIDER: S-EPMC7210479 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature