Exp Mol Med.  2009 Jul;41(7):453-461. 10.3858/emm.2009.41.7.050.

14-3-3epsilon protein increases matrix metalloproteinase-2 gene expression via p38 MAPK signaling in NIH3T3 fibroblast cells

• Lee EK
• Lee YS
• Lee H
• Choi CY
• Park SH

• KMID: 1058019
• DOI: http://doi.org/10.3858/emm.2009.41.7.050

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.

Keyword

14-3-3 proteins; extracellular matrix; matrix metalloproteinase 2; p38 mitogen-activated protein kinases; signal transduction; skin aging

MeSH Terms

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