KP1 is a peptide representing the sequence Phe57 to Lys86 of the anti aging protein Klotho, and is one of the buried beta-strands in the N-terminal domain. KP1 mimics the anti-fibrotic action of Klotho by constraining TGF-beta signaling, KP1 acts through binding to TGF-beta receptor 2 (TbetaR2) and disrupting TGF-beta/TbetaR2 interaction. KP1 inhibits multiple downstream TGF-beta pathways including activation of Smad2/3 and mitogen activated protein kinases. In mouse models of renal fibrosis, KP1 preserves kidney function, ameliorates renal fibrosis and restores endogenous Klotho expression.
