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

• Published in: Archives of biochemistry and biophysics Vol. 583; pp. 55 - 64
• Main Authors: Boteanu, Raluca Maria, Uyy, Elena, Suica, Viorel Iulian, Antohe, Felicia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2015
• Subjects: AKT1; Animals; beta Catenin - metabolism; Cell Nucleus - metabolism; Diabetes mellitus; Diabetes Mellitus, Experimental - complications; HMGB1; HMGB1 Protein - physiology; Lung; Mass Spectrometry; Mice; Mice, Transgenic; Phosphorylation; Pneumonia - complications; Pneumonia - metabolism; Pneumonia - physiopathology; Proteome; Proto-Oncogene Proteins c-akt - metabolism; RAGE; Receptor for Advanced Glycation End Products - metabolism; β-Catenin; AKT1; β-Catenin; HMGB1; RAGE; Diabetes mellitus; Lung
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2015.07.020

Diabetes mellitus generates metabolic changes associated with inflammatory events that may eventually affect all body tissues. Both high-mobility group box 1 (HMGB1) and β-catenin are active players in inflammation. The study aimed to determine whether HMGB1 modulates the β-catenin activity in supporting inflammation, using an experimental type 1 diabetes mouse model. The protein and gene expression of HMGB1 were significantly increased (2-fold) in the diabetic lung compared to control and were positively correlated with the HMGB1 levels detected in serum. Co-immunoprecipitation of HMGB1 with RAGE co-exists with activation of PI3K/AKT1 and NF-kB signaling pathways. At the same time β-catenin was increased in nuclear fraction (3.5 fold) while it was down-regulated in diabetic plasma membrane (2-fold). There was no difference of β-catenin gene expression between the control and diabetic mice. β-Catenin phosphorylation at Ser552 was higher in diabetic nuclear fraction, suggesting that AKT1 activation promotes β-catenin nuclear translocation. In addition, c-Jun directly binds β-catenin indicating the transcriptional activity of β-catenin in diabetes, sustained by significantly COX2 increase by 6-fold in the cytosolic extract of diabetic lung compared to control. Taken together, the data support the new concept that HMGB1 maintains the inflammation through RAGE/AKT1/β-catenin pathway in the diabetic lung. [Display omitted] •In type I diabetes the lung tissue showed HMGB1 protein overexpression.•β-Catenin nuclear activity was significantly increased in diabetic nuclear fraction.•HMGB1 maintains diabetic lung inflammation through RAGE/AKT1/β-catenin pathway.