Targeted delivery of type I TGF-β receptor-mimicking peptide to fibrotic kidney for improving kidney fibrosis therapy via enhancing the inhibition of TGF-β1/Smad and p38 MAPK pathways

Renal fibrosis is a representative pathological feature of various chronic kidney diseases, and efficient treatment is needed. Interstitial myofibroblasts are a key driver of kidney fibrosis, which is dependent on the binding of TGF-β1 to type I TGF-β receptor (TβRI) and TGF-β1-related signaling pathways. Therefore, attenuating TGF-β1 activity by competing with TGF-β1 in myofibroblasts is an ideal strategy for treating kidney fibrosis. Recently, a novel TβRI-mimicking peptide RIPΔ demonstrated a high affinity for TGF-β1. Thus, it could be speculated that RIPΔ may be used for anti-fibrosis therapy. Platelet-derived growth factor β receptor (PDGFβR) is highly expressed in fibrotic kidney. In this study, we found that target peptide Z-RIPΔ, which is RIPΔ modified with PDGFβR-specific affibody Z