Targeting delivery of a novel TGF-β type I receptor-mimicking peptide to activated hepatic stellate cells for liver fibrosis therapy via inhibiting the TGF-β1/Smad and p38 MAPK signaling pathways

Excessive transforming growth factor β1 (TGF-β1) secreted by activated hepatic stellate cells (aHSCs) aggravates liver fibrosis via over-activation of TGF-β1-mediated signaling pathways in a TGF-β type I receptor (TβRI) dependent manner. TβRI with the C-terminal valine truncated (RIPΔ), as a novel TβRI-mimicking peptide, is an appealing anti-fibrotic candidate by competitive binding of TGF-β1 to block TGF-β1 signal transduction. Platelet-derived growth factor receptor β (PDGFβR) is highly expressed on the surface of aHSCs in liver fibrosis. Herein, we designed a novel RIPΔ variant Z-RIPΔ (PDGFβR-specific affibody Z