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Thymosin β 4 promotes matrix metalloproteinase expression during wound repair
Author(s) -
Philp Deborah,
Scheremeta Brooke,
Sibliss Kedesha,
Zhou Min,
Fine Esther L.,
Nguyen Mychi,
Wahl Larry,
Hoffman Matthew P.,
Kleinman Hynda K.
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20650
Subject(s) - wound healing , matrix metalloproteinase , extracellular matrix , metalloproteinase , fibroblast , thymosin , western blot , microbiology and biotechnology , secretion , angiogenesis , biology , chemistry , immunology , cancer research , biochemistry , in vitro , gene
Immobilized patients, diabetics, and the elderly suffer from impaired wound healing. The 43‐amino acid angiogenic peptide thymosin β 4 (Tβ 4 ) has previously been found to accelerate dermal wound repair in rats, aged mice, and db/db diabetic mice. It also promotes corneal repair in both normal rats and mice. Because proteinases are important in wound repair, we hypothesized that Tβ 4 may regulate matrix metalloproteinase (MMP) expression in cells that are involved in wound repair. Analysis by RT‐PCR of whole excised mouse dermal wounds on days 1, 2, and 3 after wounding showed that Tβ 4 increased several metalloproteinases, including MMP‐2 and ‐9 expression by several‐fold over control on day 2 after wounding. We further analyzed the metalloproteinases secreted in response to exogenous Tβ 4 by cells normally present in the wound. Western blot analysis of cultured keratinocytes, endothelial cells, and fibroblasts that were treated with increasing concentrations of Tβ 4 showed increases in the levels of MMP‐1, ‐2, and ‐9 in a cell‐specific manner. Tβ 4 also enhanced the secretion of MMP‐1 and MMP‐9 by activated monocytes. The central actin‐binding domain, amino acids 17–23, had all of the activity for metalloproteinase induction. We conclude that part of the wound healing activity of Tβ 4 resides in its ability to increase proteinase activity via its central actin‐binding domain. Thus, Tβ 4 may play a pivotal role in extracellular matrix remodeling during wound repair. J. Cell. Physiol. © 2006 Wiley‐Liss, Inc.