Related Experiment Video
Updated: May 24, 2025
Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection
Published on: May 10, 2024
MiR-146a Reduces Inflammation in Experimental Pancreatitis via the TRAF6-NF-κB Signaling Pathway in Mice
Xiaoyu Yang1, Yuping Ren2, Xueyang Li1
1Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Background:
The initial inflammatory response plays a pivotal role in the development of acute pancreatitis. MiR-146a is believed to play a key role in negatively regulating inflammation and potentially contributes to anti-inflammatory activity in acute pancreatitis, though its mechanism remains largely unexplored.
Objectives:
This study aimed to explore the effects of miR-146a on AP in mice and clarify its regulatory mechanisms in pancreatic inflammation and damage.
Methods:
Adult male BALB/C mice were used. Adeno-associated virus (AAV) vectors were used to modulate miR-146a expression in mice via tail vein injection. AP was induced by intraperitoneal injection of caerulein, caerulein + LPS, or l-arginine. Histological analysis, immunohistochemistry staining, immunofluorescence staining, measurements of amylase and lipase activities, and qRT-PCR were performed.
Results:
Overexpression of miR-146a reduced pancreatic damage and inflammation in caerulein-induced AP. It decreased serum amylase and lipase levels, mitigated pathological features such as interstitial edema and inflammatory cell infiltration in the pancreas and lung, and reduced neutrophil infiltration and proinflammatory cytokine expression. MiR-146a attenuated the activation of the NF-κB signaling pathway by inhibiting the degradation of IκBα and the expression of phosphorylated-p65 and reducing the nuclear translocation of NF-κB p65. Similar protective effects of miR-146a were observed in AP models induced by l-arginine and caerulein combined with LPS.
Conclusions:
MiR-146a alleviates acute pancreatitis in mice by targeting TRAF6 and suppressing the activation of the NF-κB signaling pathway. These findings suggest that miR-146a could be a potential therapeutic target for AP.
Insights
MicroRNA-146a (miR-146a) alleviates acute pancreatitis (AP) in mice by reducing inflammation and pancreatic damage. This suggests miR-146a is a potential therapeutic target for AP.
Area of Science:
- Molecular Biology
- Immunology
- Gastroenterology
Background:
- Acute pancreatitis (AP) involves an initial inflammatory response.
- MicroRNA-146a (miR-146a) is implicated in negative inflammation regulation but its role in AP is unclear.
Purpose of the Study:
- To investigate the effects of miR-146a on AP in mice.
- To elucidate the mechanisms by which miR-146a regulates pancreatic inflammation and damage.
Main Methods:
- Adeno-associated virus (AAV) vectors were used to modulate miR-146a expression in mice.
- AP was induced using caerulein, caerulein + LPS, or l-arginine.
- Analyses included histology, protein expression, enzyme activity, and gene expression (qRT-PCR).
Main Results:
- Overexpression of miR-146a reduced pancreatic damage and inflammation in AP models.
- miR-146a decreased serum amylase and lipase, mitigated pathological features, and reduced inflammatory markers.
- miR-146a suppressed NF-κB pathway activation by inhibiting IκBα degradation and p65 phosphorylation.
Conclusions:
- MiR-146a alleviates AP in mice by targeting TRAF6 and inhibiting NF-κB signaling.
- MiR-146a demonstrates potential as a therapeutic target for acute pancreatitis.
