14-3-3epsilon protein increases matrix metalloproteinase-2 gene expression via p38 MAPK signaling in NIH3T3 fibroblast cells.
10.3858/emm.2009.41.7.050
- Author:
Eun Kyung LEE
1
;
Youn Sook LEE
;
Hansol LEE
;
Cheol Yong CHOI
;
Seok Hee PARK
Author Information
1. Department of Biological Science, Sungkyunkwan University, Suwon 440-746, Korea. parks@skku.edu
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
14-3-3 proteins;
extracellular matrix;
matrix metalloproteinase 2;
p38 mitogen-activated protein kinases;
signal transduction;
skin aging
- MeSH:
14-3-3 Proteins/*physiology;
Animals;
Electrophoretic Mobility Shift Assay;
Gene Expression Regulation, Enzymologic/*physiology;
Matrix Metalloproteinase 2/antagonists & inhibitors/*genetics/metabolism;
Mice;
NIH 3T3 Cells;
Plasmids;
Promoter Regions, Genetic;
RNA, Messenger/genetics/metabolism;
RNA, Small Interfering/pharmacology;
Reverse Transcriptase Polymerase Chain Reaction;
*Signal Transduction;
Transfection;
p38 Mitogen-Activated Protein Kinases/*metabolism
- From:Experimental & Molecular Medicine
2009;41(7):453-461
- CountryRepublic of Korea
- Language:English
-
Abstract:
One of the 14-3-3 protein isoforms, 14-3-3epsilon, was previously shown to be increased during skin aging. We suggest here a possible role for the 14-3-3epsilon protein in skin aging by providing evidence that 14-3-3epsilon increases the expression of the matrix-metalloproteinase (MMP)-2 gene in NIH3T3 fibroblast cells. Expression of the 14-3-3epsilon gene in NIH3T3 cells primarily up-regulated the expression of the MMP-2 gene at the transcriptional level by inducing specific DNA binding proteins bound to an upstream region of the MMP-2 promoter from -1,629 to -1,612. Inhibition of endogenous 14-3-3epsilon gene expression by RNA interference also decreased endogenous MMP-2 gene expression. Furthermore, up-regulation of the MMP-2 gene by 14-3-3epsilon was suppressed by expression of a dominant-negative mutant of p38 MAP kinase. These findings strongly suggest that increased expression of 14-3-3epsilon contributes to remodeling of extracellular matrix in skin through increasing MMP-2 gene expression via p38 MAP kinase signaling.
