Myristoyl Tetrapeptide-12 promotes dermal papilla cell proliferation and modulates wnt/β-catenin signaling and androgen receptor conformational dynamics
Abstract
IntroductionDermal 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).MethodsHuman 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.ResultsMT12 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-β1, 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.DiscussionMT12 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.
Related
- Anethole suppresses proliferation and migration of lung adenocarcinoma cells and modulates ESRβ/SRC/EGFR-related signaling
- Quercetin modulates key biomarkers and inhibits cell proliferation in endometriosis
- Targeting P2Y₁₄R inhibits proliferation of cervical cancer cells and organoids and activates cAMP/PKA/CREB signaling pathway.
- Pharmacological TLR4 Activation Promotes Hepatocyte Proliferation and Liver Repair Through Coordinated IL-6 and TCDCA Signaling.
- Miltirone suppresses proliferation and induces apoptosis in ovarian cancer cells in association with modulation of the RBM15/E2F2/PI3K/Akt signaling axis
BibTeX
@article{liu2026myristoyl,
title = {{Myristoyl Tetrapeptide-12 promotes dermal papilla cell proliferation and modulates wnt/β-catenin signaling and androgen receptor conformational dynamics}},
author = {Jianing Liu and Di Wu and Mengya Zhou and Xia Zhao and Hexiang Mei and Chuanpeng Ren and Yanyun Ma},
journal = {Frontiers in Pharmacology},
year = {2026},
month = nov,
doi = {10.3389/fphar.2026.1996340},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1996340},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Myristoyl Tetrapeptide-12 promotes dermal papilla cell proliferation and modulates wnt/β-catenin signaling and androgen receptor conformational dynamics
AU - Jianing Liu
AU - Di Wu
AU - Mengya Zhou
AU - Xia Zhao
AU - Hexiang Mei
AU - Chuanpeng Ren
AU - Yanyun Ma
PY - 2026
DA - 2026/11/09
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1996340
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1996340
AB - IntroductionDermal 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).MethodsHuman 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.ResultsMT12 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-β1, 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.DiscussionMT12 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.
SN - 1663-9812
ER -