Tissue stiffness, latent TGF-beta1 activation, and mechanical signal transduction: implications for the pathogenesis and treatment of fibrosis.
Tissue stiffening is a predominant feature of fibrosis and it obstructs organs whose mechanical properties are important for their function, such as the heart, lung, skin, and vessels. Stiff scar tissue further modulates the character of the healthy residing cells by driving the differentiation of a variety of precursor cells into fibrogenic myofibroblasts. This mechanical cue for myofibroblast differentiation establishes a vicious cycle because the excessive extracellular matrix-secreting and remodeling activities of myofibroblasts are cause and effect of further connective tissue contracture and stiffening. The second pivotal factor inducing myofibroblast development is transforming growth factor-beta1. Recent findings suggest that transforming growth factor-beta1 activity is partly controlled by myofibroblast contractile forces and tissue stiffness. This discovery opens new paths to prevent progression of fibrosis by specifically interfering with the stress perception and transmission mechanisms of the myofibroblast.
Hinz
Boris
B
CIHR Group in Matrix Dynamics, Fitzgerald Building, Room 241, University of Toronto, 150 College Street, Toronto, Ontario M5S 3E2, Canada. boris.hinz@utoronto.ca
D002921:Cicatrix / Q000473:pathology / Q000503:physiopathology; D004548:Elasticity / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000628:therapy; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D053773:Transforming Growth Factor beta1