Induction of Fibroblast-to-Myofibroblast Differentiation by Changing Cytoplasmic Actin Ratio

Abstract

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 the induced differentiation of human fibroblasts into myofibroblasts through downregulation of the γ-cytoplasmic actin (γ-CYA) achieved by RNA interference. A decrease in the γ-CYA expression in human subcutaneous fibroblasts resulted in 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, characterized by a significant increase in cell area and the formation of pronounced supermature focal adhesions. Downregulation of γ-CYA resulted in the compensatory increase in expression of the β-cytoplasmic actin and α-SMA, and formation of the characteristic α-SMA-positive stress fibers. In conclusion, our results demonstrate that a decrease in the γ-CYA expression leads to myofibroblastic trans-differentiation of human subcutaneous fibroblasts.