S100A11 Promotes Acute Pancreatitis by Upregulating Acinar Cell Ferroptosis.

Area of Science:

• Gastroenterology
• Cell Biology
• Biochemistry

Background:

• Acute pancreatitis (AP) is a gastrointestinal disease causing systemic inflammation and organ damage.
• Ferroptosis, a regulated cell death pathway, exacerbates AP progression by modulating oxidative stress and inflammation.
• S100A11 expression is elevated in AP and may play a role in disease pathogenesis.

Purpose of the Study:

• To investigate the role of S100A11 in regulating ferroptosis during acute pancreatitis.
• To determine the effect of S100A11 knockdown on pancreatic acinar cell viability and ferroptosis markers.
• To evaluate the in vivo impact of S100A11 inhibition on AP-induced ferroptosis.

Main Methods:

• Tandem mass spectrometry (TMT) proteomics identified S100A11 upregulation in an AP rat model.
• Lentiviral-mediated S100A11 knockdown was performed in caerulein-treated AR42J pancreatic acinar cells.
• Adeno-associated virus (AAV) was used for in vivo S100A11 knockdown in the AP rat model.

Main Results:

• S100A11 knockdown in vitro increased cell viability and glutathione (GSH) levels.
• S100A11 knockdown reduced reactive oxygen species (ROS), lipid ROS, and Fe²⁺ levels in pancreatic acinar cells.
• In vivo, S100A11 knockdown inhibited caerulein-induced ferroptosis in the AP rat model.

Conclusions:

• S100A11 promotes acute pancreatitis by upregulating ferroptosis.
• Targeting S100A11 may represent a novel therapeutic strategy for managing AP.
• S100A11 exacerbates AP-related oxidative stress and inflammation through ferroptosis.