Premium
Engineering Epidermal Growth Factor Mutant Proteins for Wound Healing
Author(s) -
Beck Stayce Elizabeth,
Ly Daphne,
Lee Stephen,
Longaker Michael,
Yang George,
Cochran Jennifer
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a251-a
Subject(s) - wound healing , epidermal growth factor , mutant , microbiology and biotechnology , fibroblast , biology , growth factor , receptor , medicine , immunology , in vitro , biochemistry , gene
Over 7 million people in the US and UK are afflicted by non‐healing wounds and ulcers associated with diabetes mellitus and aging. Epidermal growth factor (EGF) regulates a signaling pathway responsible for directing proliferation and differentiation in many cell types, and is one of the major proteins involved in the re‐epitheliaziation and remodeling phase of wound healing. While EGF has been shown to be effective in enhancing the wound healing process, it has an in vivo half‐life of minutes, limiting its clinical effectiveness. To address this limitation, we used directed evolution to engineer EGF mutants with a 4–30 fold increase in receptor binding affinity. The biological efficacy of these mutants was assessed using directional and chemotactic cell migration assays. Treating human and mouse fibroblast cells with mutant EGF significantly increased their ability to close an artificial wound and to migrate in response to growth factor compared to cells treated with wild‐type EGF. These results suggest potential therapeutic applications for these engineered EGF proteins in wound healing. Future work will involve testing the EGF mutants in a diabetic wound healing mouse model.