Escin Activates Canonical Wnt/β-Catenin Signaling Pathway by Facilitating the Proteasomal Degradation of Glycogen Synthase Kinase-3β in Cultured Human Dermal Papilla Cells

Author:

Shin Jae Young1ORCID,Kim Jaeyoon1ORCID,Choi Yun-Ho1ORCID,Lee Sanghwa2,Kang Nae-Gyu1

Affiliation:

1. LG Household & Health Care (LG H&H) R&D Center, 70, Magokjoongang 10-ro, Gangseo-gu, Seoul 07795, Republic of Korea

2. Innovo Therapeutics Inc., 507 38, Mapo-daero, Mapo-gu, Seoul 04174, Republic of Korea

Abstract

Abnormal inactivation of the Wnt/β-catenin signaling pathway is involved in skin diseases like androgenetic alopecia, vitiligo and canities, but small-molecule activators are rarely described. In this study, we investigated the stimulatory effects of escin on the canonical Wnt/β-catenin signaling pathway in cultured human dermal papilla cells (hDPCs). Escin stimulated Wnt/β-catenin signaling, resulting in increased β-catenin and lymphoid enhancer-binding factor 1 (LEF1), the accumulation of nuclear β-catenin and the enhanced expression of Wnt target genes in cultured hDPCs. Escin drastically reduced the protein level of glycogen synthase kinase (GSK)-3β, a key regulator of the Wnt/β-catenin signaling pathway, while the presence of the proteasome inhibitor MG-132 fully restored the GSK-3β protein level. The treatment of secreted frizzled-related proteins (sFRPs) 1 and 2 attenuated the activity of escin in Wnt reporter assays. Our data demonstrate that escin is a natural agonist of the canonical Wnt/β-catenin signaling pathway and downregulates GSK-3β protein expression by facilitating the proteasomal degradation of GSK-3β in cultured hDPCs. Our data suggest that escin likely stimulates Wnt signaling through direct interactions with frizzled receptors. This study underscores the therapeutic potential of escin for Wnt-related diseases such as androgenetic alopecia, vitiligo and canities.

Funder

LG Household & Health Care

Publisher

MDPI AG

Subject

Microbiology (medical),Molecular Biology,General Medicine,Microbiology

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