Abstract
The binding of elastin peptides on the elastin receptor complex leads to the formation of intracellular signals but how this is achieved remains totally unknown. Using pharmacological inhibitors of the enzymatic activities of its subunits, we show here that the elastin peptide-driven ERK1/2 activation and subsequent pro-MMP-1 production, observed in skin fibroblasts when they are cultured in the presence of these peptides, rely on a membrane-bound sialidase activity. As lactose blocked this effect, the elastin receptor sialidase subunit, Neu-1, seemed to be involved. The use of a catalytically inactive form of Neu-1 and the small interfering RNA-mediated decrease of Neu-1 expression strongly support this view. Finally, we report that N-acetyl neuraminic acid can reproduce the effects of elastin peptides on both ERK1/2 activation and pro-MMP-1 production. Altogether, our results indicate that the enzymatic activity of the Neu-1 subunit of the elastin receptor complex is responsible for its signal transduction, presumably through sialic acid generation from undetermined substrates.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cells, Cultured
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Elastin / metabolism
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Elastin / pharmacology
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Enzyme Activation / drug effects
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Enzyme Activation / physiology
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Fibroblasts / cytology
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Fibroblasts / metabolism*
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Gene Expression Regulation, Enzymologic / drug effects
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Gene Expression Regulation, Enzymologic / physiology
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Humans
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Lactose / pharmacology
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MAP Kinase Signaling System / drug effects
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MAP Kinase Signaling System / physiology*
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Matrix Metalloproteinase 1 / biosynthesis
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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N-Acetylneuraminic Acid / metabolism
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N-Acetylneuraminic Acid / pharmacology
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Neuraminidase / metabolism*
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Peptides / metabolism
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Peptides / pharmacology
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Protein Subunits / metabolism
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Receptors, Cell Surface / agonists
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Receptors, Cell Surface / metabolism*
Substances
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Peptides
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Protein Subunits
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Receptors, Cell Surface
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elastin-binding proteins
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Elastin
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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NEU1 protein, human
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Neuraminidase
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Matrix Metalloproteinase 1
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N-Acetylneuraminic Acid
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Lactose