Manipulation of Wnt/β-Catenin Signaling by Synthetic Frizzled Agonist and LRP Antagonist in Organoid Cultures and In Vivo.

ABSTRACT: Wnt/β-catenin signaling and its dysregulation play critical roles in stem cell fate determination and the pathology of various diseases. However, the application of translated Wnt ligand in regenerative medicine is hampered by its hydrophobicity and cross-reactivity with Frizzled (FZD) receptors. Here, a synthetic key receptor modulator, the FZD agonist RRP-pbFn is generated, for high-efficiency Wnt/β-catenin signaling activation in the absence of direct binding to LRP5/6. RRP-pbFn demonstrates superior potency compared to surrogate Wnt, supporting the growth of diverse mouse and human organoids and inducing the expansion of liver and intestine progenitors in vivo. Complementing this, a synthetic LRP antagonist, RRP-Dkk1c is developed, which exhibits heightened effectiveness in attenuating

SUBMITTER: Dai Q 

PROVIDER: S-EPMC12825328 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature