097 Thymosin β4 promotes matrix metalloproteinase expression during wound repair

Impaired wound healing is a problem for immobilized patients, diabetics, and the elderly. The 43 amino acid angiogenic peptide thymosin β4 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 β4 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 β4 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 β4 resides in its ability to increase protease activity. Since thymosin β4-induced protease activity can be further controlled by inflammatory cytokines, a regulatory role for thymosin β4 is proposed in wound healing. These studies suggest that thymosin β4 may play a pivotal role in extracellular matrix remodeling during wound repair and may be effective in the treatment of chronic wounds in humans.