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Overview
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Disrupts TGF-?/T?R2 interaction.
KP1 is a peptide representing the sequence Phe57 to Lys86 of the anti-aging protein Klotho, and is one of the buried ?-strands in the N-terminal domain. KP1 mimics the anti-fibrotic action of Klotho by constraining TGF-? signaling, KP1 acts through binding to TGF-? receptor 2 (T?R2) and disrupting TGF-?/T?R2 interaction. KP1 inhibits multiple downstream TGF-? 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.
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