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High glucose enhances MMP‐2 production in adventitial fibroblasts via Akt1‐dependent NF‐κB pathway
Author(s) -
Lee Seung Jin,
Bae Sun Sik,
Kim Koan Hoi,
Lee Won Suk,
Rhim Byung Yong,
Hong Ki Whan,
Kim Chi Dae
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.07.058
Subject(s) - matrix metalloproteinase , chemistry , pi3k/akt/mtor pathway , akt1 , nf κb , activator (genetics) , protein kinase b , electrophoretic mobility shift assay , nfkb1 , endocrinology , medicine , signal transduction , microbiology and biotechnology , transcription factor , biology , biochemistry , receptor , gene
To understand the role of adventitial fibroblasts (AF) in diabetic vascular diseases, the importance of high glucose (HG, 25 mM) 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.