The elastin peptides-mediated induction of pro-collagenase-1 production by human fibroblasts involves activation of MEK/ERK pathway via PKA- and PI(3)K-dependent signaling.
Elastin peptides, such as kappa-elastin (kE), bind to the elastin receptor at the cell surface of human dermal fibroblasts and stimulate collagenase-1 expression at the gene and protein levels. Using specific inhibitors and phosphospecific antibodies, we show here that the binding of elastin peptides to their receptor activates the extracellular signal-regulated kinase (ERK) pathway; this activation is essential for the induction of pro-collagenase-1 production. Moreover, protein kinase A (PKA) and phosphatidylinositol 3-kinase (PI(3)K) signaling were found to participate in ERK activation. Concomitantly, we demonstrate that stimulation by elastin peptides leads to enhanced DNA binding of activator protein-1 (AP-1). Our data indicate that the up-regulation of collagenase-1 following treatment of fibroblasts with elastin peptides results from a cross-talk between PKA, PI(3)K and the ERK signaling pathways and that this regulation is accompanied by activation of AP-1 transcription factors.
Université de Reims Champagne-Ardenne, FRE CNRS 2534, IFR53 Biomolécules, UFR Sciences Exactes et Naturelles et UFR Médecine, Laboratoire de Biochimie, Moulin de la Housse, Reims, France.
Laurent
L
Duca
Laurent
L
Debelle
Romain
R
Debret
Frank
F
Antonicelli
William
W
Hornebeck
Bernard
B
Haye
D000328:Adult; D017364:Collagenases / Q000096:biosynthesis*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004549:Elastin / Q000737:chemistry / Q000378:metabolism*; D004790:Enzyme Induction; D004792:Enzyme Precursors / Q000096:biosynthesis*; D005347:Fibroblasts / Q000201:enzymology*; D006801:Humans; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism
D004792:Enzyme Precursors; D010455:Peptides; D018808:Transcription Factor AP-1; D004549:Elastin; D019869:Phosphatidylinositol 3-Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D017364:Collagenases; C022440:procollagenase