Thymosin β4 enhances repair by organizing connective tissue and preventing the appearance of myofibroblasts

Abstract

Incisional wounds in rats treated locally with thymosin beta4 (Tbeta4) healed with minimal scaring and without loss in wound breaking strength. Treated wounds were significantly narrower in width. Polarized light microscopy treated wounds had superior organized collagen fibers, displaying a red birefringence, which is consistent with mature connective tissue. Control incisions had randomly organized collagen fibers, displaying green birefringence that is consistent with immature connective tissue. Immunohistology treated wounds had few myofibroblasts and fibroblasts with alpha smooth muscle actin (SMA) stained stress fibers. Polyvinyl alcohol sponge implants placed in subcutaneous pockets received either carrier or 100 microg of Tbeta4 on days 2, 3, and 4. On day 14, treated implants revealed longer, thicker collagen fiber bundles with intense yellow-red birefringence by polarized light microscopy. In controls, fine, thin collagen fiber bundles were arranged in random arrays with predominantly green birefringence. Controls contained mostly myofibroblasts, while few myofibroblasts appeared in Tbeta4 treated implants. Electron microscopy confirmed both cell types and the degree of collagen fiber bundle organization. Our results demonstrate that Tbeta4 treated wounds appear to mature earlier and heal with minimal scaring.

Thymosin β4 protects C57BL/6 mice from bleomycin‐induced damage in the lung

“…As it has been demonstrated that Tβ4 reduces phosphorylation of AKT in hepatic stellate cells and considering that we recently demonstrated a crucial role of the PI3K/AKT signalling pathway in the transformation of human lung fibroblasts into fibrotic myofibroblasts , one can hypothesize that the Tβ4 anti‐inflammatory/‐fibrogenic effect in the lung can be similarly mediated. On the other hand, it was shown that Tβ4 enhances wound repair and healing with minimal scaring by preventing the appearance of myofibroblasts . In future studies, we will elucidate the molecular mechanisms and signalling pathways involved in the protection from lung damage and putatively fibrosis afforded by Tβ4.…”

“…preventing the appearance of myofibroblasts [19]. In future studies, we will elucidate the molecular mechanisms and signalling pathways involved in the protection from lung damage and putatively fibrosis afforded by Tb4.…”

A novel dimeric thymosin beta 4 with enhanced activities accelerates the rate of wound healing

“…Tβ4 has been found to have considerable and broad biological activities, including promoting the migration of endothelial cells,4 accelerating angiogenesis,5,6 downregulating inflammatory responses,7,8 and inhibiting apoptosis and oxidative damage 9,10. Tβ4 also can organize the distribution of collagen by reducing the presence of myofibroblasts in the wound area 11. Angiogenesis is deemed as the most important mechanism for Tβ4-induced cutaneous wound healing and cardioprotection 12,13.…”

Thymosin β4 affecting the cytoskeleton organization of the myofibroblasts

“…However, as previously reported vanadate-and thymosin beta 4 (T␤4)-treated wounds do not contain myofibroblasts, yet wound contraction is unaffected by their absence. 3,4 Thus, the question arises: is the absence of ␣SMA-enriched stress fibers in myofibroblasts within granulation tissue a direct effect of T␤4 or an indirect effect?…”

“…In contrast, PVA implants treated with T␤4 showed collagen fibers arranged in uniform arrays. 4 To begin to address the question of whether inhibition of the transformation of fibroblasts into myofibroblasts by T␤4 is a direct effect on fibroblasts or an indirect effect involving the activity of other cells, we are investigating T␤4 in cell culture for its ability to transform myofibroblasts back into fibroblasts.…”