کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2515680 | 1118543 | 2013 | 10 صفحه PDF | دانلود رایگان |

Impaired wound healing and skin aging are characterized by neutral protease-mediated destruction of matrix macromolecules associated with disturbance in tissue repair. We synthesized a fatty acyl-peptide derivative at aims to simultaneously activate latent TGF-β through its peptide domain, KFK, and inhibit MMPs through its lipophilic moiety, elaidic acid. Elaidyl-KFK as well as KFK were shown to activate LAP-TGF-β both in vitro, using a solid phase assay with immobilized LAP-TGF-β, and ex vivo using human dermal fibroblasts cultures. In both assays, as much as up to 10% of LAP-TGF-β added could be recovered as active form. KQK, KQFK as well as their lipopeptide counterparts were inactive. Elaidyl-KFK-mediated LAP-TGF-β activation led to up-regulation of collagen and TIMP-1 production and down regulation of PMA-induced MMP-1 expression in fibroblasts cultures. Those effects could be suppressed by supplementing cell culture medium with blocking TGF-β antibody. Elaidyl-KFK inhibited MMP-2, MMP-9, MMP-3, MMP-1, in vitro with IC50 equal to 1.2, 1.0, 0.24 and 8.9 μM, respectively. Its ex vivo inhibitory capacity, as assessed using skin tissue sections, towards the elastin-degrading capacity of MMP-9 was even more pronounced. At a 1 μM concentration, the lipopeptide decreased by up to 80% enzyme activity. Thus, “Lipospondin,” i.e. elaidyl-KFK might be considered as a promising model compound to prevent age-associated dermal alterations.
Journal: Biochemical Pharmacology - Volume 67, Issue 11, 1 June 2004, Pages 2013–2022