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

Authors :
Lee SJ
Bae SS
Kim KH
Lee WS
Rhim BY
Hong KW
Kim CD
Source :
FEBS letters [FEBS Lett] 2007 Sep 04; Vol. 581 (22), pp. 4189-94. Date of Electronic Publication: 2007 Aug 03.
Publication Year :
2007

Abstract

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.

Details

Language :
English
ISSN :
0014-5793
Volume :
581
Issue :
22
Database :
MEDLINE
Journal :
FEBS letters
Publication Type :
Academic Journal
Accession number :
17692316
Full Text :
https://doi.org/10.1016/j.febslet.2007.07.058