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T. Meyer-ter-Vehn, H. Han, F. Grehn, G. Schlunck; Extracellular Matrix Rigidity Modulates TGF-β-Induced Myofibroblast Transdifferentiation. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4153.
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Matrix rigidity and the cytokine TGF-β influence scar formation in an interdependent fashion. Here we study the impact of variant matrix rigidity on TGF-β-induced myofibroblast transdifferentiation and signal transduction.
Primary human tenon fibroblasts were seeded on fibronectin-coated glass cover slips (rigid environment) or fibronectin-coated collagen or polyacrylamid gels of variant compliance and stimulated with TGF-β. Myofibroblast transdifferentiation was assessed by real time PCR and western blot for the marker gene α-smooth muscle actin (SMA) and its incorporation into stress fibers by immunofluorescence. Signaling pathways were examined by western blot using phosphospecific antibodies and immunofluorescence.
TGF-β-driven myofibroblast transdifferentiation depends on a stiff environment. Increasing matrix compliance attenuates TGF-β-induced myofibroblast transdifferentiation. On the level of signal transduction a soft matrix mitigates TGF-β-induced p38 activation whereas SMAD signalling is not affected.
Our results suggest that matrix stiffness critically governs myofibroblast transdifferentiation and therefore represent an important determinant of scarring processes. Mechanical aspects as matrix rigidity and their impact on cellular responses should be taken into account in modern antifibrotic strategies.
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