Conformational Dependence of Collagenase (Matrix Metalloproteinase-1) Up-regulation by Elastin Peptides in Cultured Fibroblasts - Archive ouverte HAL Access content directly
Journal Articles Journal of Biological Chemistry Year : 2001

Conformational Dependence of Collagenase (Matrix Metalloproteinase-1) Up-regulation by Elastin Peptides in Cultured Fibroblasts

, (1) , (2) , , (3) , (4) , (5) , (6) , (7) , (8) ,
1
2
3
4
5
6
7
8

Abstract

We have established that treatment of cultured human skin fibroblasts with tropoelastin or with heterogenic peptides, obtained after organo-alkaline or leukocyte elastase hydrolysis of insoluble elastin, induces a high expression of pro-collagenase-1 (pro-matrix metalloproteinase-1 (pro-MMP-1)). The identical effect was achieved after stimulation with a VGVAPG synthetic peptide, reflecting the elastin-derived domain known to bind to the 67-kDa elastin-binding protein. This clearly indicated involvement of this receptor in the described phenomenon. This notion was further reinforced by the fact that elastin peptides-dependent MMP-1 up-regulation has not been demonstrated in cultures preincubated with 1 mm lactose, which causes shedding of the elastin-binding protein and with pertussis toxin, which blocks the elastin-binding protein-dependent signaling pathway involving G protein, phospholipase C, and protein kinase C. Moreover, we demonstrated that diverse peptides maintaining GXXPG sequences can also induce similar cellular effects as a "principal" VGVAPG ligand of the elastin receptor. Results of our biophysical studies suggest that this peculiar consensus sequence stabilizes a type VIII beta-turn in several similar, but not identical, peptides that maintain a sufficient conformation to be recognized by the elastin receptor. We have also established that GXXPG elastin-derived peptides, in addition to pro-MMP-1, cause up-regulation of pro-matrix metalloproteinase-3 (pro-stromelysin 1). Furthermore, we found that the presence of plasmin in the culture medium activated these MMP proenzymes, leading to a consequent degradation of collagen substrate. Our results may be, therefore, relevant to pathobiology of inflammation, in which elastin-derived peptides bearing the GXXPG conformation (created after leukocyte-dependent proteolysis) bind to the elastin receptor of local fibroblasts and trigger signals leading to expression and activation of MMP-1 and MMP-3, which in turn exacerbate local connective tissue damage.

Dates and versions

hal-02328935 , version 1 (23-10-2019)

Identifiers

Cite

Bertrand Brassart, Patrick Fuchs, Eric Huet, Alain Alix, Jean Wallach, et al.. Conformational Dependence of Collagenase (Matrix Metalloproteinase-1) Up-regulation by Elastin Peptides in Cultured Fibroblasts. Journal of Biological Chemistry, 2001, 276 (7), pp.5222-5227. ⟨10.1074/jbc.M003642200⟩. ⟨hal-02328935⟩
52 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More