High-mobility group box 1 enhances the inflammatory process in diabetic lung

Area of Science:

• Immunology
• Endocrinology
• Molecular Biology

Background:

• Diabetes mellitus induces metabolic changes and widespread inflammation.
• High-mobility group box 1 (HMGB1) and β-catenin are implicated in inflammatory processes.

Purpose of the Study:

• To investigate the role of HMGB1 in modulating β-catenin activity within the context of inflammation in type 1 diabetes.
• To elucidate the signaling pathways involved in HMGB1-mediated inflammation in a diabetic mouse model.

Main Methods:

• Utilized an experimental type 1 diabetes mouse model.
• Measured protein and gene expression of HMGB1 and β-catenin.
• Performed co-immunoprecipitation to assess protein interactions and pathway activation (PI3K/AKT1, NF-kB).

Main Results:

• HMGB1 levels were significantly elevated in the lungs and serum of diabetic mice.
• HMGB1 interacted with RAGE, activating PI3K/AKT1 and NF-kB signaling.
• β-catenin translocated to the nucleus, with increased phosphorylation, and directly bound c-Jun, correlating with COX2 upregulation.

Conclusions:

• HMGB1 promotes inflammation in the diabetic lung via the RAGE/AKT1/β-catenin signaling axis.
• This pathway involves β-catenin nuclear translocation and activation of downstream inflammatory mediators like COX2.