Thymosin β4 affecting the cytoskeleton organization of the myofibroblasts

In previous studies, granulation tissue from subcutaneous sponge implants in rats receiving thymosin β4, a 43-amino acid actin-binding protein that advances wound repair, produced the unexpected absence of myofibroblast populations, along with uniform organized collagen fibers within the newly deposited connective tissue matrix. This result raised the question of whether the Tβ4 effect on blocking fibroblasts transformation into myofibroblasts a direct or indirect one. We report here work in progress to address this question. When human dermal fibroblasts are plated at low density, upon reaching confluence, they all express α smooth muscle actin (αSMA) within their cytoplasmic stress fibers, morphologically defining them as myofibroblasts. Treating low-density plated fibroblasts with Tβ4 prevents their expression of αSMA, as well as the generation an uneven distribution of microtubules within the cytoplasm. The speculation is that Tβ4 disruption of the distribution of microtubules alters the TGF-β-Smad signaling pathway, thus blocking fibroblast transformation into myofibroblasts.