Xiaoyu Yang, Yuping Ren, Xueyang Li, Liang Xia, Jianhua Wan
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引用次数: 0
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.
期刊介绍:
Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including:
• cellular and molecular immunology
• clinical immunology
• allergy
• immunochemistry
• immunogenetics
• immune signalling
• immune development
• imaging
• mathematical modelling
• autoimmunity
• transplantation immunology
• cancer immunology