title: High-mobility group box 1 enhances the inflammatory process in diabetic lung.
abstract: 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.
authors.affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu", 8 BP Hasdeu Street, PO Box 35-14, 050568, Bucharest, Romania.
authors.forename: Raluca Maria
authors.initials: RM
authors.lastname: Boteanu
authors.affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu", 8 BP Hasdeu Street, PO Box 35-14, 050568, Bucharest, Romania.
authors.forename: Elena
authors.initials: E
authors.lastname: Uyy
authors.affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu", 8 BP Hasdeu Street, PO Box 35-14, 050568, Bucharest, Romania.
authors.forename: Viorel Iulian
authors.initials: VI
authors.lastname: Suica
authors.affiliation: Institute of Cellular Biology and Pathology "Nicolae Simionescu", 8 BP Hasdeu Street, PO Box 35-14, 050568, Bucharest, Romania. Electronic address: felicia.antohe@icbp.ro.
authors.forename: Felicia
authors.initials: F
authors.lastname: Antohe
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D024243:HMGB1 Protein / Q000502:physiology*; D013058:Mass Spectrometry; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D011014:Pneumonia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D020543:Proteome; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C000593873:Ager protein, mouse; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D020543:Proteome; D000067759:Receptor for Advanced Glycation End Products; D051176:beta Catenin; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT1; Diabetes mellitus; HMGB1; Lung; RAGE; β-Catenin