MiR-146a Reduces Inflammation in Experimental Pancreatitis Via the TRAF6-NF-κB Signaling Pathway in Mice

Overview

Journal Immun Inflamm Dis

Specialties Allergy & Immunology
Infectious Diseases

Date 2025 Feb 28

PMID 40018991

Authors

Xiaoyu Yang

Yuping Ren

Xueyang Li

Liang Xia

Jianhua Wan

Affiliations

Soon will be listed here.

Abstract

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.

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