Mechanical aspects of lung fibrosis: a spotlight on the myofibroblast.
Contractile myofibroblasts are responsible for the irreversible alterations of the lung parenchyma that hallmark pulmonary fibrosis. In response to lung injury, a variety of different precursor cells can become activated to develop myofibroblast features, most notably formation of stress fibers and expression of α-smooth muscle actin. Starting as an acute and beneficial repair process, myofibroblast secretion of collagen and contraction frequently becomes excessive and persists. The result is accumulation of stiff scar tissue that obstructs and ultimately destroys lung function. In addition to being a consequence of myofibroblast activities, the stiffened tissue is also a major promoter of the myofibroblast. The mechanical properties of scarred lung and fibrotic foci promote myofibroblast contraction and differentiation. One essential element in this detrimental feed-forward loop is the mechanical activation of the profibrotic growth factor transforming growth factor-β1 from stores in the extracellular matrix. Interfering with myofibroblast contraction and integrin-mediated force transmission to latent transforming growth factor-β1 and matrix proteins are here presented as possible therapeutic strategies to halt fibrosis.
Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, 150 College Street, Toronto, Ontario, Canada. boris.hinz@utoronto.ca
Boris
B
Hinz
D002454:Cell Differentiation; D049109:Cell Proliferation; D002921:Cicatrix / Q000503:physiopathology; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism; D058628:Myofibroblasts / Q000378:metabolism* / Q000473:pathology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000378:metabolism / Q000503:physiopathology*; D022502:Stress Fibers / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014945:Wound Healing
D039001:Integrin alpha Chains; D053773:Transforming Growth Factor beta1