Tadalafil curbs lung fibrosis in rats by blocking epithelial-mesenchymal transition through a PKG-HDAC2 route
- In rat models of lung fibrosis induced by bleomycin or paraquat, daily tadalafil lessened fibrosis and lung injury, including when treatment began at an advanced stage.
- Benefit appeared to run through cGMP/PKG signalling, dampening TGF-β/Smad activity and epithelial-mesenchymal transition.
- Preliminary data point to PKG lowering HDAC2; silencing or inhibiting HDAC2 mimicked the drug, while overexpressing it reversed the effect. The authors suggest clinical evaluation for repurposing.
💡 Points Based on the abstract
Tadalafil's appeal is a known human safety profile, but PDE5 inhibitors have already been tried in fibrotic lung disease with modest signal, so the rat data need to beat that history. Bleomycin and paraquat resolve spontaneously and poorly mimic human IPF; I'd want exposure at the efficacious dose compared with human levels, plus HDAC2 and EMT readouts in patient-derived lung fibroblasts or tissue.