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Publication : High glucose enhances MMP-2 production in adventitial fibroblasts via Akt1-dependent NF-kappaB pathway.

First Author  Lee SJ Year  2007
Journal  FEBS Lett Volume  581
Issue  22 Pages  4189-94
PubMed ID  17692316 Mgi Jnum  J:125112
Mgi Id  MGI:3723558 Doi  10.1016/j.febslet.2007.07.058
Citation  Lee SJ, et al. (2007) High glucose enhances MMP-2 production in adventitial fibroblasts via Akt1-dependent NF-kappaB pathway. FEBS Lett 581(22):4189-94
abstractText  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-kappaB) were enhanced by HG, but NF-kappaB were not increased in 1KO cells. Furthermore, HG-induced MMP-2 responses were markedly suppressed by NF-kappaB decoy oligodeoxynucleotides. Based on these results, it is suggested that HG augments MMP-2 production via PI3K/Akt1/NF-kappaB pathway.
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