Pancreatic Elastase Affects Liver Injury by Activating Proinflammatory Cytokines in Kupffer Cells via the JAK2/STAT3 Signaling Pathway
Year: 2025
Type: article
Abstract: INTRODUCTION: This study aimed to investigate the role of JAK2 (Janus kinase 2)/STAT3 (signal transducer and activator of transcription 3) signaling in liver injury during severe acute pancreatitis (SAP), focusing on pancreatic elastase- and lipopolysaccharide (LPS)-induced Kupffer cell (KC) activation. METHODS: A rat SAP model was established via retrograde taurocholic acid infusion into the biliopancreatic duct. Inflammatory cytokine levels and JAK2/STAT3 pathway activity were quantified in liver tissues. KCs were treated with elastase/LPS ± AG490 (JAK2 inhibitor). Proinflammatory cytokines, RNA, and protein expression were analyzed. RESULTS AND DISCUSSION: SAP rats exhibited elevated TNF-α, IL-6, and IL-18 levels in both serum and liver tissues, with JAK2/STAT3 pathway activation. AG490 administration suppressed JAK2/STAT3 activation, reduced inflammation, and alleviated liver injury. Similarly, KCs treated with elastase and LPS showed increased proinflammatory cytokine levels and JAK2/STAT3 upregulation, which were mitigated by AG490 treatment. CONCLUSION: The findings highlighted the pivotal role of the JAK2/STAT3 signaling pathway in SAP-induced liver injury. Selective inhibition of this pathway by AG490 could reduce inflammation and protect against liver damage, suggesting its potential as a therapeutic target for inflammatory liver diseases.
Source: Current Molecular Medicine
Authors: Ying Feng, Xinxin Jin, Haoyu Xu, Bo Sun, Meixia Guo, Minli Li
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4411951978