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Myristoyl Tetrapeptide-12 promotes dermal papilla cell proliferation and modulates wnt/β-catenin signaling and androgen receptor conformational dynamics

Year: 2026

Type: article

Abstract: Introduction Dermal papilla cells regulate hair follicle growth, yet bioactive peptides that influence both pro-growth signaling and androgen receptor (AR)-associated regulation remain poorly characterized. This study evaluated the effects of Myristoyl Tetrapeptide-12 (MT12) on human dermal papilla cell function and its potential interaction with the AR ligand-binding domain (AR-LBD). Methods Human dermal papilla cells were treated with MT12, with bicalutamide as a pharmacological reference. Cell viability, proliferation, and expression of Wnt/ β -catenin-related, AR-associated, and hair-growth-related genes were assessed by CCK-8, EdU incorporation, and quantitative PCR, respectively. Molecular docking, 500-ns molecular dynamics simulations, and residue communication-network analysis were used to characterize MT12–AR-LBD interactions. Results MT12 showed good cytocompatibility and significantly increased dermal papilla cell proliferation, with EdU-positive cells increasing from approximately 5% in controls to 18%–22% after treatment. MT12 increased CTNNB1 and WNT5A expression and reduced DKK1 expression, together with changes in AR , TGF- β 1 , and PEDF/SERPINF1 transcripts. Computational analyses indicated that MT12 remained associated with the AR-LBD binding pocket and altered local flexibility, conformational sampling, correlated residue motions, and intradomain communication. A recurrent ASN705–MET895–ILE898 route linked the ligand-binding region to the H12/AF-2 regulatory region. Discussion MT12 promotes dermal papilla cell proliferation and induces a Wnt/ β -catenin-related transcriptional profile consistent with pro-growth signaling, while structural analyses suggest modulation of AR conformational dynamics. These integrated cellular and computational findings support MT12 as a potential modulator of dermal papilla cell function, although AR-related activity and the causal role of Wnt/ β -catenin signaling require further validation.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1996340