Comparison of the effects of serpin A1, a recombinant serpin A1-IGF chimera and serpin A1 C-terminal peptide on wound healing.
Serpin A1 (alpha1-antitrypsin, alpha1-proteinase inhibitor), a potent neutrophil elastase inhibitor, has therapeutic potential as a wound-healing agent. We compared the in vitro wound-healing action of serpin A1-IGF, a recombinant fusion protein of serpin A1(M351E-M358L) and insulin-like growth factor I with that observed in the presence of natural serpin A1 or A1-C26, the synthetic C-terminal 26 residue peptide of serpin A1, previously shown to have mitogenic and antiviral activities. All agents reduced wound sizes in monolayers of the kidney epithelial cell line LLC-PK1 and in primary cultures of human skin fibroblasts. Wound reduction in primary human keratinocytes was only observed with the serpin A1-IGF chimera. None of the factors stimulated cell proliferation using a colorimetric assay, with the exception of the serpin A1-IGF chimera, which caused a significant increase of cell proliferation and thymidine incorporation in human skin fibroblasts. However, wound healing by the A1-IGF chimera was reduced in keratinocytes in the presence of mitomycin C, suggesting a role of cell proliferation in wound reduction. The hydrophobic A1-C26 peptide significantly increased the production of collagen I in skin fibroblasts, an appealing asset for skin care applications.
Endocrine Laboratory, McGill University Health Centre, 687 avenue des pins, Ouest, Montreal, Canada H3A 1A1. luis.f.congote@muhc.mcgill.ca <luis.f.congote@muhc.mcgill.ca>
Luis Fernando
LF
Congote
Nyssa
N
Temmel
Gulzhakhan
G
Sadvakassova
Monica C
MC
Dobocan
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004847:Epithelial Cells / Q000187:drug effects; D005347:Fibroblasts / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007334:Insulin-Like Growth Factor I / Q000737:chemistry / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012867:Skin / Q000737:chemistry; D013552:Swine; D014945:Wound Healing / Q000187:drug effects*; D000515:alpha 1-Antitrypsin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D024042:Collagen Type I; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D000515:alpha 1-Antitrypsin; D007334:Insulin-Like Growth Factor I