# The Muscarinic Acetylcholine Receptor in Dermal Papilla Cells Regulates Hair Growth

## TL;DR

This study shows that the muscarinic acetylcholine receptor in skin cells regulates hair growth through specific signaling pathways.

## Contribution

The study identifies the M4 muscarinic receptor as a key regulator of hair growth via Wnt/β-catenin signaling in dermal papilla cells.

## Key findings

- Inhibiting AChE or activating mAChR promotes hair growth in cultured cells and mouse skin.
- Activation of Wnt/β-catenin signaling occurs through PI3K/AKT and ERK pathways upon mAChR stimulation.
- Treatment with bethanechol increases hair shaft elongation in mouse vibrissae.

## Abstract

The role of cholinergic system in hair biology is poorly understood. In M4 muscarinic receptor (mAChR) knockout mice, the hair follicles have a prolonged telogen phase and fail to produce hair shafts. Here, we reported that hair growth was regulated by cholinergic signalling via mAChRs. Dermal papilla cells expressed different cholinergic biomarkers. Inhibiting AChE or activating mAChR in dermal papilla cells, cultured vibrissae and mouse skin epidermis promoted the hair growth. In cultured papilla cells treated with bethanechol, an agonist of mAChR, an activation of Wnt/β-catenin signalling was illustrated by various indicative biomarkers, including phosphorylation of GSK-3β and mRNA expression of various molecules for Wnt/β-catenin signalling. Activation of Wnt/β-catenin signalling was mediated by PI3K/AKT and ERK signalling upon the stimulation of bethanechol. Moreover, the bethanechol-mediated signalling was blocked by specific antagonist of M4 mAChR. In addition, an increase in hair shaft elongation was observed in mouse vibrissae upon the treatment of bethanechol, suggesting the cholinergic role in hair growth.