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KMID : 0620920090410070453
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Experimental & Molecular Medicine
2009 Volume.41 No. 7 p.453 ~ p.461
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14-3-3ε protein increases matrix metalloproteinase-2 gene expression via p38 MAPK signaling in NIH3T3 fibroblast cells
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Lee Eun-Kyung
Lee Youn-Sook
Lee Han-Sol
Choi Cheol-Yong
Park Seok-Hee
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Abstract
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One of the 14-3-3 protein isoforms, 14-3-3ε, was previously shown to be increased during skin aging. We suggest here a possible role for the 14-3-3ε protein in skin aging by providing evidence that 14-3-3ε increases the expression of the matrix-metalloproteinase (MMP)-2 gene in NIH3T3 fibroblast cells. Expression of the 14-3-3ε 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 14-3-3ε gene expression by RNA interference also decreased endogenous MMP-2 gene expression. Furthermore, up-regulation of the MMP-2 gene by 14-3-3ε was suppressed by expression of a dominant-negative mutant of p38 MAP kinase. These findings strongly suggest that increased expression of 14-3-3ε contributes to remodeling of extracellular matrix in skin through increasing MMP-2 gene expression via p38 MAP kinase signaling.
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KEYWORD
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14-3-3 proteins, extracellular matrix, matrix metalloproteinase 2, p38 mitogen-activated protein kinases, signal transduction, skin aging
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