VMP1 Constitutive Expression in Mice Dampens Pancreatic and Systemic Histopathological Damage in an Experimental Model of Severe Acute Pancreatitis
Abstract
1. Introduction
2. Results
2.1. Intrapancreatic Features
2.1.1. ElaI-VMP1 Mice Exhibit Lower Serum Enzyme Concentrations, Reduced Inflammatory Signs, and Less Necrosis During Experimental SAP
- Edema Analysis
- Inflammatory Infiltration
- Acinar Necrosis
- Fat Necrosis and Hemorrhage
2.1.2. ElaI-VMP1 Mice Exhibit Higher Levels of Zymophagy, Which Significantly Correlates with Lower Acinar Necrosis During Experimental SAP
2.2. Extrapancreatic Features
ElaI-VMP1 Mice Exhibited Preserved Liver Histology, Normal Kidney Histoarchitecture, and Clean Lung Tissue During Experimental SAP
- Liver
- Kidneys
- Lungs
3. Discussion
4. Materials and Methods
- Mice
- Transgenic Mice (ElaI-VMP1 Mice)
- CAE/EK-induced Pancreatitis Model
- Biochemical Markers
- Histological Studies
- ○
- Pancreatic Tissue
- ○
- Extra-pancreatic Tissue Damage
- Liver Damage: At LPF (i.e., 40×), the presence and localization of necrotic areas (e.g., centrilobular) were considered. At HPF, histological evidence of loss of hepatocyte membrane integrity, signs of tissue necrosis (e.g., cytoplasm swelling and/or intracellular vacuoles), and areas of leukocyte infiltration, especially in centrilobular areas, were examined;
- Kidney Damage: Kidney damage was assessed by examining areas of acute tubular necrosis with patchy loss of tubular epithelial cells, desquamation, pyknosis, and loss of nuclei, as well as the presence of intraluminal cellular debris;
- Lung Damage: For lung damage evaluation, particular emphasis was placed on septal integrity and thickness, as well as hemorrhagic foci in the alveolar spaces. The presence of leukocyte infiltration was noted, though it was not the central focus of the lung damage assessment.
- Antibodies
- IF Assays
- Statistics
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ANOVA | Analysis of Variance |
AP | Acute Pancreatitis |
CAE | Caerulein |
CCK | Cholecystokinin |
CCK-R | Cholecystokinin Receptor |
EK | Enterokinase |
ElaI-VMP1 | C57BL6J-ElaI-VMP1 transgenic mice |
FXR | Farnesoid X receptor |
H&E | Hematoxylin and Eosin |
HPF | High-Power Field |
IF | Immunofluorescence |
IQR | Interquartile Range |
Lamp2 | Lysosome-Associated Membrane Glycoprotein 2 |
LC3 | Microtubule-Associated Protein 1A/1B-light chain 3 |
LDH | Lactate Dehydrogenase |
LPF | Low-Power Field |
mTOR | Mammalian Target of Rapamycin |
mTORC1 | Mammalian Target of Rapamycin Complex 1 |
NF-κB | Nuclear Transcription Factor-κB |
NS | Non-Significant |
Osgin1 | Oxidative Stress-Induced Growth Inhibitor 1 |
PBS | Phosphate-Buffered Saline |
S6K1 | Serine/threonine Kinase 1 |
SAP | Severe Acute Pancreatitis |
SD | Standard Deviation |
SEM | Standard Error of the Mean |
VMP1 | Vacuole Membrane Protein 1 |
WT | Wild-Type |
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Histopathological Score | 0 | 1 | 2 | 3 | 4 |
---|---|---|---|---|---|
Edema | Absent | Diffuse expansion of Interlobar septae | “1” + Diffuse expansion of Interlobular septae | “2” + Diffuse expansion of Interacinar septae | “3” + Diffuse expansion of intercellular spaces |
Inflammation and perivascular infiltrate | 0–5 intralobular or perivascular leukocytes/HPF | 6–15 intralobular or perivascular leukocytes/HPF | 16–25 intralobular or perivascular leukocytes/HPF | 26–35 intralobular or perivascular leukocytes/HPF | >35 intralobular or perivascular leukocytes/HPF |
Acinar necrosis | Absent or Focal occurrence of 0–4 necrotic cells/HPF | Diffuse occurrence of 0–4 necrotic cells/HPF or Focal occurrence of 5–10 necrotic cells/HPF | Diffuse occurrence of 5–10 necrotic cells/HPF or Focal occurrence of 11–16 necrotic cells/HPF | Diffuse occurrence of 11–16 necrotic cells/HPF or Focal occurrence of >16 necrotic cells/HPF | >16 necrotic cells/HPF |
Hemorrhage and fat necrosis | Absent | 1–3 foci | 4–5 foci | 6–7 foci | ≥8 foci |
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Boggio, V.; Gonzalez, C.D.; Zotta, E.; Ropolo, A.; Vaccaro, M.I. VMP1 Constitutive Expression in Mice Dampens Pancreatic and Systemic Histopathological Damage in an Experimental Model of Severe Acute Pancreatitis. Int. J. Mol. Sci. 2025, 26, 3196. https://doi.org/10.3390/ijms26073196
Boggio V, Gonzalez CD, Zotta E, Ropolo A, Vaccaro MI. VMP1 Constitutive Expression in Mice Dampens Pancreatic and Systemic Histopathological Damage in an Experimental Model of Severe Acute Pancreatitis. International Journal of Molecular Sciences. 2025; 26(7):3196. https://doi.org/10.3390/ijms26073196
Chicago/Turabian StyleBoggio, Veronica, Claudio Daniel Gonzalez, Elsa Zotta, Alejandro Ropolo, and Maria Ines Vaccaro. 2025. "VMP1 Constitutive Expression in Mice Dampens Pancreatic and Systemic Histopathological Damage in an Experimental Model of Severe Acute Pancreatitis" International Journal of Molecular Sciences 26, no. 7: 3196. https://doi.org/10.3390/ijms26073196
APA StyleBoggio, V., Gonzalez, C. D., Zotta, E., Ropolo, A., & Vaccaro, M. I. (2025). VMP1 Constitutive Expression in Mice Dampens Pancreatic and Systemic Histopathological Damage in an Experimental Model of Severe Acute Pancreatitis. International Journal of Molecular Sciences, 26(7), 3196. https://doi.org/10.3390/ijms26073196