Related Experiment Video
Updated: Feb 19, 2026
Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection
Published on: May 10, 2024
TGM2 Aggravates Acute Pancreatitis by Impairing Macrophage Efferocytosis Through Inhibition of the STAT6-GAS6 Axis
Xuxu Liu1, Zhiwei Du1, Liyi Wang1
1Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Background:
Acute pancreatitis (AP) is characterized by dysregulated inflammation, with macrophage dysfunction (impaired efferocytosis, pro/anti-inflammatory phenotype imbalance) exacerbating the disease. Current therapies are mostly supportive, highlighting the critical need for targeted interventions.
Methods:
Transglutaminase 2 (TGM2) was identified via public transcriptomic analysis. Its function was validated in caerulein-induced AP mice and in vitro cell models; mechanisms were explored via Co-IP, ChIP, and dual-luciferase assays. A lactoferrin-modified, ROS-responsive LF-LNP system was developed for TGM2 siRNA delivery.
Results:
TGM2 was upregulated in AP; its inhibition alleviated pancreatic injury and inflammation. Mechanistically, TGM2 bound STAT6 to suppress its phosphorylation/nuclear translocation, downregulating efferocytosis-related GAS6 and impairing macrophage efferocytosis. LF-LNP@si-TGM2 targeted pancreatic macrophages, silenced TGM2, restored the STAT6-GAS6 axis, enhanced efferocytosis, and reduced inflammation.
Conclusion:
This study identifies TGM2 as a key regulator of AP macrophage efferocytosis via the novel TGM2-STAT6-GAS6 axis. LF-LNP@si-TGM2 is a promising targeted strategy for AP, potentially shifting treatment from supportive to precision therapy.
Related Concept Videos
01:30Acute Pancreatitis II: Clinical Manifestations and Management
01:24Chronic Pancreatitis I: Introduction
Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...
01:27Acute Pancreatitis I: Introduction
Acute pancreatitis is characterized by rapid inflammation of the pancreas, often caused by factors like gallstone blockage or excessive alcohol consumption. Chronic pancreatitis, on the other hand, is a slow, progressive inflammation that may result from long-term alcohol abuse, obstructions in the pancreatic duct, or genetic factors.
The causes of acute pancreatitis include:
01:29Chronic Pancreatitis II: Collaborative Care
Assessment:
01:17Gastritis-II: Pathophysiology
In acute gastritis, the gastric mucosa becomes swollen and red and undergoes superficial erosion. Superficial ulceration may lead to bleeding.
In chronic gastritis, persistent or repeated insults lead to chronic inflammatory changes and, eventually, thinning or atrophy of the gastric tissue.
Gastritis can stem from various causes, each...
01:09GPCRs Regulate Adenylyl Cylase Activity