The elastin peptides‐mediated induction of pro‐collagenase‐1 production by human fibroblasts involves activation of MEK/ERK pathway via PKA‐ and PI3K‐dependent signaling

FEBS Letters

Antonicelli, Frank¹  Hornebeck, William¹  Duca, Laurent¹  Debelle, Laurent¹  Haye, Bernard¹  Debret, Romain¹ 

[1] 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, P.O. Box 1039, 51687 Reims Cedex 2, France

关键词: Fibroblast;    κ-Elastin;    Collagenase-1;    Mitogen-activated protein kinase/extracellular signal-regulated kinase;    Activator protein-1;    Protein kinase A;    Phosphatidylinositol 3-kinase;    AP-1;    activator protein-1;    CREB;    cAMP response-element-binding protein;    DMEM;    Dulbecco's modified Eagle's medium;    EBP;    elastin-binding protein;    ERK;    extracellular signal-regulated kinase;    kE;    κ-elastin;    MAP kinase;    mitogen-activated protein kinase;    MEK;    MAP/ERK kinase;    MMP-1;    matrix metalloproteinase-1 or collagenase-1;    NF-κB;    nuclear factor κB;    pERK;    phosphorylated ERK;    PI3K;    phosphatidylinositol 3-kinase;    PKA;    protein kinase A;    PKC;    protein kinase C;   

DOI  :  10.1016/S0014-5793(02)03057-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 (PI₃K) 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, PI₃K and the ERK signaling pathways and that this regulation is accompanied by activation of AP-1 transcription factors.

【 授权许可】

Unknown