Why the study?
Models generating quantitative data on 3D fibroblast-mediated ECM remodeling with the reproducibility and throughput needed for drug testing were lacking.
Does inhibition of specific signaling pathways (e.g., MEK, ROCK, LOX) reduce TGFβ-induced 3D ECM remodeling in primary human fibroblasts?
Population
TGFβ-activated primary human skin or lung fibroblasts
Design
Preclinical in vitro compound screening assay development study
Key result
Non-canonical activation of MEK-ERK signaling drives fibrotic ECM remodeling, and high concentrations of TGFβ receptor inhibitors paradoxically stimulate this MEK-mediated profibrotic activity.
Authors
Loading...
High-dose TGFβ inhibitors may paradoxically promote fibrosis; leaves open MEK-ERK targeting in cardiac fibrotic remodeling.
Does inhibition of specific signaling pathways (e.g., MEK, ROCK, LOX) reduce TGFβ-induced 3D ECM remodeling in primary human fibroblasts?
A novel 3D high-throughput assay reveals that non-canonical MEK-ERK signaling drives fibrotic ECM remodeling and that high doses of TGFβ receptor inhibitors paradoxically stimulate this profibrotic activity.
Liao et al. (2025) studied Fibrosis. MEK inhibitors and TGFβ receptor inhibitors vs. Control medium was evaluated on ECM remodeling between fibroblast clusters. Non-canonical activation of MEK-ERK signaling drives fibrotic ECM remodeling, and high concentrations of TGFβ receptor inhibitors paradoxically stimulate this MEK-mediated profibrotic activity.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: