miR-148a and miR-551b-5p regulate inflammatory responses via regulating autophagy in acute pancreatitis

Area of Science:

• Biochemistry
• Molecular Biology
• Immunology

Background:

• Acute pancreatitis (AP) is a severe inflammatory condition with high mortality and limited effective treatments.
• MicroRNAs (miRNAs) are implicated in AP pathogenesis, particularly via the IL-6 signaling pathway.
• Understanding the precise mechanisms of miRNA involvement is crucial for developing novel therapeutic strategies.

Purpose of the Study:

• To investigate the role and underlying mechanisms of exosomal miR-148a and miR-551b-5p in acute pancreatitis.
• To explore the potential of these miRNAs as diagnostic markers and therapeutic targets for AP.

Main Methods:

• Exosomes were isolated from peripheral blood mononuclear cells of AP patients and healthy volunteers.
• MicroRNA expression levels (miR-148a, miR-551b-5p) were analyzed.
• Pancreatic acinar cells (PACs) were transfected to overexpress miR-148a/miR-551b-5p to assess their functional impact on autophagy and inflammatory cytokine secretion.

Main Results:

• Both miR-148a and miR-551b-5p showed significantly higher expression in AP patients compared to healthy controls.
• Overexpression of miR-551b-5p in PACs promoted autophagy by targeting BIRC6, increasing IL-1β and IL-18 secretion via the IL-1 signaling pathway.
• Overexpression of miR-148a in PACs reduced IL-1β and IL-18 secretion and modulated autophagy.
• Exosomal miR-148a and miR-551b-5p were found to mediate autophagy damage through the IL-6/STAT3 signaling pathway in AP pathogenesis.

Conclusions:

• Exosomal miR-148a and miR-551b-5p play a dual role in modulating autophagy and inflammation in acute pancreatitis.
• These miRNAs are potential biomarkers for AP diagnosis and novel therapeutic targets.
• Targeting these exosomal miRNAs may offer a new avenue for AP treatment.