Controlling the Mechanical Myofibroblast via SRC: A Potential Drug Discovery Platform

Connective tissue makes up a large portion of our bodies, with collagen constituting ∼30% of the protein of connective tissue. Any tissue that undergoes fibrosis, either due to a genetic mutation or with age or use, typically falls into the ubiquitous category of ‘connective tissue fibrosis’. There are multiple potential contributors to connective tissue fibrosis; however, two dominate the literature — mechanical stress/strain and cytokines. Both stimuli lead to activation of fibroblast cells to a myofibroblast phenotype, the cellular hallmark of fibrotic disease. The myofibroblast phenotype is indicated by the expression of smooth muscle α-actin (αSMA), which associates with myosin to form actin-myosin contractile elements and generates intracellular force that is transduced to the ECM via cell membrane integrins.