[Cytochalasin B-Induced adipose stem cell-derived nanovesicles promote hair follicle regeneration via activation of the β-catenin signaling pathway].

Objectives

To evaluate the regulatory effects of adipose stem cell (ADSC)-derived cytochalasin B-induced nanovesicles (CINVs) on the biological functions of dermal papilla cells (DPCs) and on hair follicle cycle transition, and to explore the underlying molecular mechanisms.

Methods

CINVs were prepared from ADSCs. Their effects on DPC proliferation, migration, and apoptosis were assessed in vitro. A mouse depilation model was used to evaluate the ability of CINVs to promote the transition of hair follicles from telogen to anagen. Western blotting, hematoxylin-eosin (HE) staining, and immunofluo-rescence analyses were performed to assess the activation of β-catenin-related signaling pathways and to elucidate the molecular mechanisms of CINV-mediated hair follicle regeneration.

Results

CCK-8 assays showed that CINVs at 40 and 60 μg/mL significantly enhanced DPC proliferation. Wound healing assays (at 40 μg/mL) confirmed that CINVs markedly promoted DPC migration. Western blotting revealed that, compared with the control group, CINV treatment significantly increased the expression of phosphorylated GSK-3β (p-GSK-3β, P<0.05) and upregulated β-catenin, the core effector of the canonical Wnt/β-catenin pathway (P<0.01). Moreover, cyclin D1 (a positive regulator of cell cycle progression) expression was elevated (P<0.05), and the levels of phosphorylated AKT (p-AKT, associated with cell survival) and phosphorylated ERK (p-ERK, associated with cell proliferation) were significantly increased (both P<0.05). The Bcl-2/Bax ratio (an anti-apoptotic index) was also increased. In vivo, CINV-treated mice displayed darkened dorsal skin and enlarged hair bulb diameters, along with elevated proportions of β-catenin- and Ki67-positive cells. These effects were significantly attenuated by co-administration of the β-catenin inhibitor MSAB.

Conclusions

ADSC-derived CINVs effectively regulate the biological functions of DPCs and promote the transition of hair follicles from telogen to anagen, primarily through activation of the β-catenin signaling pathway.