ECM-Stiffness Mediated Persistent Fibroblast Activation Requires Integrin and Formin Dependent Chromatin Remodeling - PubMed
6 hours ago
- #mechanotransduction
- #chromatin remodeling
- #fibroblast activation
- Fibroblasts switch from transient to persistent activation upon prolonged exposure to stiff ECMs and stiffness-dependent secreted factors.
- The persistent activation switch involves ECM-stiffness-dependent mechanotransduction pathways and changes in nuclear architecture and chromatin association.
- Two key pathways are required: β1 integrin activation smoothens the nuclear lamina and reduces lamin-chromatin contacts, while mDia2 formin activation alters lamin-chromatin coupling via nuclear actin assembly.
- Blocking either the integrin or mDia2 pathway prevents persistent myofibroblast activation, which is rescued by histone deacetylase inhibition, linking dynamic chromatin modifications to maintained activation.
- These findings connect integrin-based ECM sensing to chromatin remodeling and fibroblast memory, with implications for stromal plasticity in the tumor microenvironment.