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Updated: Nov 10, 2025
Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection
Published on: May 10, 2024
miR-339-3p regulated acute pancreatitis induced by caerulein through targeting TNF receptor-associated factor 3 in
Qi Wang1, Shaofeng Liu1, Zhen Han1
1Department of Gastroenterology, The Yijishan Hospital of Wannan Medical College, Room 505, Unit 3, Building 1, Yiyuan Community, No. 109, Tuanjie West Rd, 241001, Wuhu, Anhui, China.
Abstract:
Acute pancreatitis (AP) is an inflammatory disease with high morbidity and mortality. The regulation mechanism of miRNA is involved in the production and development of various diseases, but the regulation mechanism of miRNA in AP is still not fully elucidated. The expression of miR-339-3p was detected using quantitative real-time PCR. The levels of TNF-α, IL-1β, and IL-6 were detected using enzyme-linked immunosorbent assay. Cell apoptosis was measured using flow cytometry. The protein expressions of TNF receptor-associated factor 3 (TRAF3), Bcl-2, C-caspase 3, Bax, p-p38, and p38 were measured using western blot. Luciferase reporter assay and RNA immunoprecipitation assay were applied to ensure that miR-399-3p targeted TRAF3. Caerulein promoted the expression of TNF-α, IL-1β, and IL-6, enhanced the expression of C-caspase 3 and Bax while inhibited Bcl-2 protein expression. Meanwhile, caerulein also reduced the expression of miR-339-3p and induced the expression of TRAF3 in rat pancreatic acinar cells. miR-399-3p transfection inhibited the levels of TNF-α, IL-1β, and IL-6 and C-caspase 3 and Bax protein expression as well as suppressed cell apoptosis, while increased Bcl-2 protein expression in caerulein-induced AP. TRAF3 has been verified as a target of miR-339-3p. Interestingly, the reduction of miR-399-3p inhibited the p38 pathway, which was impaired by the upregulation of TRAF3. In addition, the suppression effects of miR-339-3p on cell inflammation and apoptosis in caerulein-induced AP were reversed by enhancing TRAF3 expression. In this study, in vitro model of AP was characterized by strong inflammation and cell apoptosis. We have first demonstrated the regulatory network of miR-339-3p and TRAF3. Overexpression of miR-339-3p inhibited cell inflammation and cell apoptosis in caerulein-induced AP through modulating TRAF3 expression via the p38 pathway, providing a new therapeutic target in the treatment of AP.
Insights
MicroRNA-339-3p (miR-339-3p) targets TRAF3 to reduce inflammation and apoptosis in acute pancreatitis (AP). This finding offers a new therapeutic strategy for treating AP by modulating the p38 pathway.
Area of Science:
- Molecular Biology
- Cell Biology
- Pathology
Background:
- Acute pancreatitis (AP) is a severe inflammatory condition with significant morbidity and mortality.
- MicroRNA (miRNA) dysregulation is implicated in various diseases, but its role in AP pathogenesis remains incompletely understood.
- Identifying novel regulatory mechanisms is crucial for developing effective AP treatments.
Purpose of the Study:
- To elucidate the regulatory role of miR-339-3p in acute pancreatitis.
- To investigate the interaction between miR-339-3p and TNF receptor-associated factor 3 (TRAF3) in AP.
- To explore the potential of miR-339-3p as a therapeutic target for AP.
Main Methods:
- Quantitative real-time PCR and enzyme-linked immunosorbent assay were used to measure miRNA and cytokine levels (TNF-α, IL-1β, IL-6).
- Flow cytometry assessed cell apoptosis, while western blot analyzed protein expression (TRAF3, Bcl-2, C-caspase 3, Bax, p38).
- Luciferase reporter and RNA immunoprecipitation assays confirmed the targeting of TRAF3 by miR-339-3p.
Main Results:
- Caerulein-induced AP models showed increased inflammation (TNF-α, IL-1β, IL-6), apoptosis (C-caspase 3, Bax), and TRAF3 expression, alongside decreased miR-339-3p and Bcl-2.
- miR-339-3p transfection significantly reduced inflammation, apoptosis, and TRAF3 levels, while increasing Bcl-2 expression in AP models.
- TRAF3 was confirmed as a direct target of miR-339-3p, and its upregulation impaired the miR-339-3p-mediated inhibition of the p38 pathway.
Conclusions:
- miR-339-3p plays a protective role in acute pancreatitis by inhibiting inflammation and apoptosis.
- The therapeutic effects of miR-339-3p involve the modulation of TRAF3 expression and the p38 signaling pathway.
- Targeting the miR-339-3p/TRAF3 axis presents a promising therapeutic avenue for acute pancreatitis treatment.
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