1. Model for TGF-β-induced myofibroblast differentiation involving MKL1 isoform-specific activities.
Model for TGF-β-induced myofibroblast differentiation involving MKL1 isoform-specific activities. On the basis of the published models that seek to explain the delayed activation of the Rho–actin–MKL1 pathway by TGF-β during myofibroblast differentiation (Sandbo et al., 2011; Masszi et al., 2010), we propose that MKL1_S is one of the factors directly induced by Smad signaling during the initial phase of differentiation. Direct activation of the Rho–actin–MKL1 pathway by a second hit and/or the indirect activation via Smad signaling and MKL1_S induction are then likely to have two consequences. First, an SRF-mediated expression of contractile smooth-muscle-specific genes such as SMA, induced by either MKL1 isoform. Second, the expression of genes coding for ECM(-modifying) proteins regulated specifically by MKL1_S. We hypothesize that MKL1_S-specific transcription contributes to the progression to the advanced phase of myofibroblast differentiation involving ECM modifications and the downregulation of migration.
Matthias A. Scharenberg et al. J Cell Sci 2014;127:
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