# VMP1 Constitutive Expression in Mice Dampens Pancreatic and Systemic Histopathological Damage in an Experimental Model of Severe Acute Pancreatitis

## TL;DR

This study shows that increased VMP1 in mice reduces pancreatic and systemic damage in severe acute pancreatitis by enhancing protective autophagy.

## Contribution

The study demonstrates that VMP1-mediated zymophagy protects against both pancreatic and extrapancreatic injury in a severe acute pancreatitis model.

## Key findings

- ElaI-VMP1 mice show reduced pancreatic necrosis, edema, and inflammation compared to wild-type mice.
- VMP1 expression preserves liver, kidney, and lung histology in a severe acute pancreatitis model.
- Increased zymophagy correlates negatively with acinar necrosis, highlighting its protective role.

## Abstract

Acute pancreatitis (AP) an inflammatory condition caused by the premature activation of pancreatic proteases, leads to organ damage, systemic inflammation, and multi-organ failure. Severe acute pancreatitis (SAP) has high morbidity and mortality, affecting the liver, kidneys, and lungs. Autophagy maintains pancreatic homeostasis, with VMP1-mediated selective autophagy (zymophagy) preventing intracellular zymogen activation and acinar cell death. This study examines the protective role of VMP1 (Vacuole Membrane Protein 1)-induced autophagy using ElaI-VMP1 transgenic mice in a necrohemorrhagic SAP model (Hartwig’s model). ElaI-VMP1 mice show significantly reduced pancreatic injury, including lower necrosis, edema, and inflammation, compared to wild-type (WT) mice. Biochemical markers (lactate dehydrogenase-LDH-, amylase, and lipase) and histopathology confirm that VMP1 expression mitigates pancreatic damage. Increased zymophagy negatively correlates with acinar necrosis, reinforcing its protective role. Beyond the pancreas, ElaI-VMP1 mice exhibit preserved liver, kidney, and lung histology, indicating reduced systemic organ damage. The liver maintains normal architecture, kidneys show minimal tubular necrosis, and lung inflammation features are reduced compared to WT mice. Our results confirm that zymophagy functions as a protective pathophysiological mechanism against pancreatic and extrapancreatic tissue injury in SAP. Further studies on the mechanism of VMP1-mediated selective autophagy in AP are necessary to determine its relevance and possible modulation to prevent the severity of AP.