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Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection
Published on: May 10, 2024
854
Rab9 Mediates Pancreatic Autophagy Switch From Canonical to Noncanonical, Aggravating Experimental Pancreatitis
Olga A Mareninova1, Dustin L Dillon1, Carli J M Wightman1
1Department of Medicine, Los Angeles, California; VA Greater Los Angeles Healthcare System, Los Angeles, California.
Cellular and Molecular Gastroenterology and Hepatology
|October 5, 2021
Summary
Rab9
Area of Science:
- Cell Biology
- Molecular Biology
- Gastroenterology
Background:
- Autophagosomes form via canonical (LC3-II) or noncanonical (Rab9) pathways.
- Canonical autophagy is vital for exocrine pancreas homeostasis; its dysfunction causes pancreatitis.
- The role of noncanonical autophagy in pancreatitis remains unexplored.
Purpose of the Study:
- To investigate the role of Rab9 in pancreatic autophagy.
- To determine Rab9's involvement in pancreatitis severity.
Main Methods:
- Used transgenic mice overexpressing Rab9 (Rab9TG) and adenoviral transduction of acinar cells.
- Assessed canonical autophagy's effect on Rab9 in ATG5-deficient acinar cells.
Main Results:
- Rab9 levels decreased in rodent and human pancreatitis models.
- Rab9 overexpression promoted noncanonical autophagy and inhibited canonical autophagy via ATG4B.
- Rab9 deficiency increased in ATG5-deficient cells; Rab9TG pancreas showed impaired canonical autophagy and pancreatitis-like damage.
Conclusions:
- Rab9 regulates pancreatic autophagy, with antagonistic canonical and noncanonical pathways.
- Noncanonical autophagy does not compensate for canonical autophagy in pancreatitis protection.
- Decreased Rab9 in pancreatitis is a protective mechanism to maintain canonical autophagy and reduce disease severity.
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