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Thymosin β 4 promotes matrix metalloproteinase expression during wound repair
Author(s) -
Philp Deborah,
Sibliss Kedesha,
Kleinman Hynda K.
Publication year - 2008
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2005.130216a.x
Subject(s) - wound healing , thymosin , matrix metalloproteinase , extracellular matrix , protease , fibroblast , western blot , chemistry , medicine , microbiology and biotechnology , immunology , biology , biochemistry , enzyme , gene , in vitro
Impaired wound healing is a problem for immobilized patients, diabetics, and the elderly. The 43 amino acid angiogenic peptide thymosin β 4 has previously been found to promote accelerated dermal wound repair in rats, aged mice and db/db diabetic mice, and corneal repair in normal rats. It has been found in great abundance in wound fluid. Here, we hypothesized that thymosin β 4 may regulate matrix metalloproteinase (MMP) expression in cells that are involved in wound repair. Western blot analysis of keratinocytes, endothelial cells, and fibroblasts that were treated with increasing concentrations of thymosin β 4 showed changes in the expression of the MMP‐1, −2, and −9. Zymographic analysis of whole excised mouse wounds taken after homogenization also showed changes in MMP‐2 and‐9 expression over a 3‐day period. These results were confirmed in 2‐day‐old wounds by RT‐PCR. We conclude that part of the wound healing activity of thymosin β 4 resides in its ability to increase protease activity. Since thymosin β 4 ‐induced protease activity can be further controlled by inflammatory cytokines, a regulatory role for thymosin β 4 is proposed in wound healing. These studies suggest that thymosin β 4 may play a pivotal role in extracellular matrix remodeling during wound repair and may be effective in the treatment of chronic wounds in humans.