Induction of fibroblast-to-myofibroblast differentiation by alteration of cytoplasmic actin ratio

Myofibroblasts, which play a crucial role in the tumour microenvironment, represent a promising avenue for research in the field of oncotherapy. This study investigates the potential for induced differentiation of human fibroblasts into myofibroblasts through the downregulation of the γ-cytoplasmic actin (γ-CYA), which was achieved by RNA interference. A decrease in γ-CYA expression in human subcutaneous fibroblasts resulted in the upregulation of myofibroblast markers, including α-smooth muscle actin (α-SMA), ED-A FN, and type III collagen. These changes were accompanied by notable alterations in cellular morphology, characterised by a significant increase in cell area and formation of pronounced supermature focal adhesions. The downregulation of γ-CYA resulted in a compensatory increase in the expression of β-cytoplasmic actin and α-SMA, and the formation of characteristic α-SMA-positive stress fibers. In conclusion, our results demonstrate that a reduction in γ-CYA expression leads to myofibroblastic trans-differentiation of human subcutaneous fibroblasts.