The role of PLIN2 gene in macrophages and its effect on Acute pancreatitis.

BACKGROUND AND

OBJECTIVE

Acute pancreatitis (AP) is a severe inflammatory disease with limited therapeutic options. This study aimed to investigate the role of Perilipin 2 (PLIN2) in macrophage polarization and its impact on AP progression.

METHODS

An AP mouse model was established using sodium taurocholate, and RAW 264.7 macrophages were differentiated with phorbol 12-myristate 13-acetate (PMA). Pancreatic acinar cells were treated with lipopolysaccharide (LPS) and caerulein (CAE). Techniques included immunohistochemistry (IHC), Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry, and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays to assess macrophage polarization, lipid deposition, and cell damage.

RESULTS

In AP, PLIN2 expression was significantly upregulated, correlating with enhanced M1 macrophage polarization and excessive lipid droplet accumulation in pancreatic tissue. Genetic knockdown of PLIN2 effectively reduced lipid deposition, suppressed pro-inflammatory M1 polarization, and promoted anti-inflammatory M2 macrophage polarization, leading to marked attenuation of pancreatic cell damage and apoptosis. Notably, these protective effects were counteracted by the overexpression of cyclic GMP-AMP synthase (cGAS), which restored lipid deposition and M1 polarization.

CONCLUSIONS

PLIN2 regulates macrophage polarization and lipid metabolism in AP, with its knockdown alleviating tissue damage by suppressing M1 polarization and promoting M2 polarization, suggesting its potential as a therapeutic target for AP management.