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High glucose enhances MMP-2 production in adventitial fibroblasts via Akt1-dependent NF-kappaB pathway.
- 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.
- Subjects :
- Animals
Connective Tissue drug effects
Enzyme Activation drug effects
Enzyme Induction drug effects
Fibroblasts drug effects
Isoenzymes metabolism
Matrix Metalloproteinase 2 genetics
Mice
Oligodeoxyribonucleotides pharmacology
Phosphatidylinositol 3-Kinases metabolism
Promoter Regions, Genetic genetics
Protein Binding drug effects
Signal Transduction drug effects
Time Factors
Transcription Factors metabolism
Transcription, Genetic drug effects
Connective Tissue enzymology
Fibroblasts enzymology
Glucose pharmacology
Matrix Metalloproteinase 2 biosynthesis
NF-kappa B metabolism
Proto-Oncogene Proteins c-akt metabolism
Subjects
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