Thymosin β₄ and a synthetic peptide containing its actin‐binding domain promote dermal wound repair in db/db diabetic mice and in aged mice

Abstract

Impaired wound healing is a problem for immobilized patients, diabetics, and the elderly. Thymosin beta 4 has previously been found to promote dermal and corneal repair in normal rats. Here we report that thymosin beta 4 was also active in accelerating wound repair in full-thickness dermal wounds in both db/db diabetic and aged mice. We found that thymosin beta 4 in either phosphate-buffered saline or a hydrogel formulation is active in promoting dermal wound repair in normal rats. In diabetic mice, where healing is delayed, we found that wound contracture and collagen deposition were significantly increased in the mice treated with thymosin beta 4 in either phosphate buffered saline solution or a hydrogel formulation. No difference was observed in keratinocyte migration, with all of the diabetic animals showing almost complete coverage of the wound at 8 days. Wound healing in 26-month-old (aged) animals was significantly delayed. Thymosin beta 4 accelerated wound healing in these aged mice, with increases in keratinocyte migration, wound contracture, and collagen deposition. The hydrogel formulation generally showed similar wound healing activity with thymosin beta 4 in PBS. The actin-binding domain of thymosin beta 4 duplicated in a seven-amino acid synthetic peptide, LKKTETQ, was able to promote repair in the aged animals comparable to that observed with the parent molecule. These studies show that thymosin beta 4 is active for wound repair in models of impaired healing and may have efficacy in chronic wounds in humans.

Thymosin β4 is involved in stabilin‐2‐mediated apoptotic cell engulfment

“…Actin is essential for cell division, cell movement, phagocytosis and differentiation. In addition, the central actin-binding site in thymosin b4 is required for its angiogenic [7] and wound-healing activity [8,9], suggesting that its interaction with actin is functionally important beyond sequestration [10].…”

Nuclear localisation of the G-actin sequestering peptide thymosin β4

“…In the extracellular space, thymosin β 4 participates in several physiological processes, e.g. angiogenesis (Grant et al, 1995;Malinda et al, 1997;Philp et al, 2003b), wound healing (Malinda et al, 1999;Sosne et al, 2001;Sosne et al, 2002;Philp et al, 2003a) and regulation of inflammation (Sosne et al, 2001;Sosne et al, 2002). We have recently shown that it also serves as a specific glutaminyl substrate of transglutaminases (Huff et al, 1999) which crosslink thymosin β 4 released from stimulated human platelets to fibrin and collagen .…”

Effects of thymosin β4 on a rat model of severe acute pancreatitis

“…Thymosin β4 has shown promising efficacy in animal models of various diseases, such as myocardial infarction, dermal wounds, multiple sclerosis, sepsis and endotoxic shock (12,20,(28)(29)(30)(31). However, to the best of our knowledge, there have been no reports concerning thymosin β4 in the treatment of acute pancreatitis until now.…”