High glucose enhances MMP-2 production in adventitial fibroblasts via Akt1-dependent NF-κB pathway

• Published in: FEBS letters 2007-09, Vol.581 (22), p.4189-4194
• Main Authors: Lee, Seung Jin, Bae, Sun Sik, Kim, Koan Hoi, Lee, Won Suk, Rhim, Byung Yong, Hong, Ki Whan, Kim, Chi Dae
• Format: Article
• Language: English
• Subjects: activator protein-1; Adventitial fibroblasts; AP-1; ECM; electrophoretic mobility shift assay; EMSA; extracellular matrix; High glucose; matrix metalloproteinase; Matrix metalloproteinase-2; MMP; NF-κB; nuclear factor-kappa B; ODN; oligodeoxynucleotides; PI3K/Akt1
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2007.07.058

To understand the role of adventitial fibroblasts (AF) in diabetic vascular diseases, the importance of high glucose (HG, 25mM) on matrix metalloproteinase-2 (MMP-2) production in AF was determined. HG enhanced mRNA, protein and gelatinolytic activity of MMP-2. The enhanced MMP-2 activity was significantly attenuated not only by a PI3K inhibitor but also by an Akt inhibitor. These HG-induced MMP-2 responses were markedly reduced in Akt1-deficient (1KO) cells. The diminished HG-induced MMP-2 responses were completely restored by re-expression of Akt1. Both the reporter activity and electrophoretic mobility shift assay for activator protein-1 and nuclear factor-kappa B (NF-κB) were enhanced by HG, but NF-κB were not increased in 1KO cells. Furthermore, HG-induced MMP-2 responses were markedly suppressed by NF-κB decoy oligodeoxynucleotides. Based on these results, it is suggested that HG augments MMP-2 production via PI3K/Akt1/NF-κB pathway.