Jul 2026· Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences· pp.
1-11
· 0 citations· 41 references
Medicine
TL;DR
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.
Abstract
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.
With the changing pace of life and increasing environmental pressures, the prevalence of hirsutism has increased. Hair follicle stem cells (HFSCs) are the starting factor and the key factor in hair follicle regeneration. In this study, we conducted in vitro and in vivo experiments to systematically examine the effects of exosome-like nanoparticles derived from leeks (LELNs) on the proliferation and differentiation of HFSCs and the underlying molecular mechanisms. LELNs promoted the proliferation and migration of HFSCs and improved their endogenous antioxidant and antibacterial capacities. In addition, LELNs inhibited the expression of NLRP3 protein in the classical pathway of HFSCs and exerted anti-inflammatory effects, which reduced the release of inflammatory factors. Furthermore, these particles inhibited hair maturation in rat models by inhibiting the Wnt/β-catenin signaling pathway and triggering HFSC differentiation into sebaceous gland cells. In conclusion, this study highlights LELNs altering HFSC differentiation direction by inhibiting the Wnt/β-catenin pathway and the potential therapeutic efficacy of LELNs in managing hirsutism.
Li Guan, Chuan-Jie Zhang, Da-Ke Wang et al.· ACS Applied Bio Materials· 0 citations
Objective: To evaluate whether human adipose-derived mesenchymal stem cells (ADSCs) protect against ᴅ-galactose (ᴅ-gal)-induced aging-like testicular injury and to investigate the involvement of the Keap1/Nrf2 pathway and NLRP3-associated pyroptosis. Methods: A mouse model of aging-like testicular injury was established by subcutaneous administration of ᴅ-gal for 8 weeks, followed by tail vein injection of ADSCs. Testicular morphology, blood–testis barrier (BTB) integrity, and senescence-associated markers (p16, p21) were assessed. In vitro, TM4 Sertoli cells were used to establish a senescence model and Tranwell co-cultured with ADSCs. Oxidative stress, inflammatory responses, and pyroptosis-related markers were evaluated using biochemical assays, immunofluorescence, Western blotting, and RT-qPCR. The involvement of the Keap1/Nrf2-NLRP3 axis was further examined using pharmacological inhibitors. Results: ADSC treatment significantly alleviated ᴅ-gal-induced testicular atrophy and histopathological injury, accompanied by reduced expression of the senescence markers p16 and p21 and partial restoration of BTB-related structures. ADSCs also attenuated oxidative stress, as evidenced by decreased ROS and MDA levels, increased SOD activity, and enhanced expression of Nrf2 and its downstream antioxidant targets, including HO-1 and NQO1. In parallel, ADSC administration suppressed NLRP3 activation, reduced caspase-1 cleavage, and lowered the expression of pro-inflammatory cytokines. In TM4 cells, inhibition of Nrf2 weakened the protective effects of ADSCs and was accompanied by reactivation of NLRP3-associated signaling, whereas inhibition of NLRP3 attenuated senescence- and inflammation-related changes without restoring Nrf2 activity. Conclusions: ADSCs alleviate ᴅ-gal-induced aging-like testicular injury, at least in part, by restoring redox balance, preserving BTB-associated structure, and suppressing NLRP3-associated pyroptosis through the Keap1/Nrf2 pathway. These findings suggest that ADSC-based therapy may represent a promising strategy for age-related male reproductive dysfunction, while further studies using genetic models and functional fertility endpoints are needed to confirm causality and translational relevance.
Mengjia He, Tianhang Yang, Songpo Liu et al.· Antioxidants· 0 citations
Hair-follicle development is a key determinant of the quality and yield of Angora rabbit wool. Vitamin E (VE) has antioxidant properties and regulates cell proliferation. However, the molecular mechanism by which VE regulates hair-follicle growth is unclear. This study investigated the effects of VE on hair follicles and dermal papilla cells (DPCs) in vitro, as well as their underlying regulatory mechanism involving long noncoding RNA (lncRNA)2919, STAT1, and the Hedgehog signaling pathway. Hair follicles and DPCs were isolated and cultured. The optimal VE concentration was determined to be 50 μM. Reverse-transcription quantitative PCR, Western blotting, and CCK-8, DNA pulldown, chromatin immunoprecipitation, and dual-luciferase reporter assays revealed that VE significantly promoted both hair-follicle growth and DPC proliferation, and also regulated the expression of hair follicle-development–related genes, such as LEF1, FGF2, TGFβ1, and SFRP2, and antioxidant genes, including SOD1 and NRF2, and also enhanced the antioxidant capacity. Mechanistically, VE significantly downregulated lncRNA2919 expression, while lncRNA2919 overexpression inhibited DPC proliferation, which was reversed by VE. Furthermore, lncRNA2919 maintained STAT1 protein levels by inhibiting the proteasome-mediated degradation pathway. STAT1 was observed to bind directly to the SHH promoter and inhibit its transcription. This effect was reversed by VE via downregulation of lncRNA2919/STAT1 and subsequent activation of the Hedgehog signaling pathway. In conclusion, VE induces the proliferation of DPCs and enhances cellular antioxidant capacity by regulating the lncRNA2919/STAT1/SHH axis, thereby promoting hair-follicle growth and development. The findings provide a novel theoretical basis for understanding hair-follicle growth and the use of VE in Angora rabbits.
Yinuo Fang, Sen Wang, Chengpeng Cao et al.· Non-coding RNA Research· 0 citations
