| First Author | Boteanu RM | Year | 2015 |
| Journal | Arch Biochem Biophys | Volume | 583 |
| Pages | 55-64 | PubMed ID | 26254814 |
| Mgi Jnum | J:230765 | Mgi Id | MGI:5763722 |
| Doi | 10.1016/j.abb.2015.07.020 | Citation | Boteanu RM, et al. (2015) High-mobility group box 1 enhances the inflammatory process in diabetic lung. Arch Biochem Biophys 583:55-64 |
| abstractText | Diabetes mellitus generates metabolic changes associated with inflammatory events that may eventually affect all body tissues. Both high-mobility group box 1 (HMGB1) and beta-catenin are active players in inflammation. The study aimed to determine whether HMGB1 modulates the beta-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 beta-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 beta-catenin gene expression between the control and diabetic mice. beta-Catenin phosphorylation at Ser552 was higher in diabetic nuclear fraction, suggesting that AKT1 activation promotes beta-catenin nuclear translocation. In addition, c-Jun directly binds beta-catenin indicating the transcriptional activity of beta-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/beta-catenin pathway in the diabetic lung. |
