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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
Author(s) -
Duca Laurent,
Debelle Laurent,
Debret Romain,
Antonicelli Frank,
Hornebeck William,
Haye Bernard
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03057-0
Subject(s) - elastin , tropoelastin , collagenase , microbiology and biotechnology , mapk/erk pathway , kinase , signal transduction , activator (genetics) , chemistry , protein kinase a , biochemistry , receptor , extracellular matrix , biology , enzyme , genetics
Elastin peptides, such as κ‐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.