Protein expression in exocrine pancreatic diseases. Focus on VMP1 mediated autophagy.

Abstract

The exocrine pancreas produces enzymes involved in the digestive process whereas endocrine pancreas mainly regulates glucose metabolism. Diseases of the exocrine pancreas are characterized by high morbidity and mortality. Acute pancreatitis is a painful disease in which pancreatic secretory proteins are prematurely activated causing the digestion of the gland. Pancreatic adenocarcinoma is one of the most malignant cancers due to its resistance to treatment, its late diagnosis and high capacity for metastasis. Autophagy is a catabolic process that aims at degrading cytoplasmic contents and damaged organelles, to preserve cell viability and homeostasis. VMP1 is a transmembrane protein that plays a key role in triggering autophagy and being part of the autophagosome membrane. A specific type of selective autophagy pathway called zymophagy protects the pancreas against self-digestion in the setting of acute pancreatitis by sequestering intracellularly activated zymogen granules. Mitophagy is also responsible for maintaining pancreatitis as a mild disease by preserving mitochondrial function. Dysregulation of these selective autophagic processes by pancreatitis itself constitutes a risk factor for development of severe disease. In pancreatic adenocarcinoma, VMP1 mediated autophagy promotes cancer cell survival and resistance to chemotherapy. Therefore, it is relevant to highlight a role for controlling VMP1 expression and targeting VMP1 molecular pathways to improve exocrine pancreatic diseases prognosis.