Preliminary exploration of ferroptosis induced by three chemical inducers in atopic dermatitis-like mouse models
10.3969/j.issn.1005-4847.2025.10.007
- VernacularTitle:三种药物诱导特应性皮炎样小鼠模型的铁死亡初探
- Author:
Wei TANG
1
;
Yuanfei XU
;
Chunmei GONG
;
Shufa WU
;
Junluan MO
;
Hui YANG
Author Information
1. 深圳市慢性病防治中心,深圳市皮肤病防治研究所,广东 深圳 518020
- Publication Type:Journal Article
- Keywords:
calcipotriol;
2,4-dinitrochlorobenzene;
oxazolone;
atopic dermatitis;
mouse model;
ferroptosis
- From:
Acta Laboratorium Animalis Scientia Sinica
2025;33(10):1463-1472
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish atopic dermatitis(AD)-like models in BALB/c mice using three chemical inducers,calcipotriol(MC903),2,4-dinitrochlorobenzene(DNCB),and oxazolone(OXA),and to explore the occurrence of ferroptosis in the different models.Methods Healthy 7-week-old female BALB/c mice were divided randomly into eight groups(n=8 mice per group)based on the induction site(ear/dorsal skin)and inducer:ear/dorsal control groups,MC903 ear/dorsal model groups,DNCB ear/dorsal model groups,and OXA ear/dorsal model groups.Models were established by topical application of the respective agents at specified concentrations.Mice in the MC903 ear/dorsal groups underwent continuous induction for 14 d.Mice in the DNCB and OXA ear/dorsal groups were sensitized for 3 consecutive days,4 days after the sensitization was completedand then challenged 12 times on day 8 and every other day for up to day 30.Skin lesions were observed and skin thickness was measured.Plasma levels of reactive oxygen species(ROS),interleukin(IL)-4,interferon(IFN)-γ,and malondialdehyde(MDA)were detected,the skin was examined by histopathological staining and ultrastructural observation,and expression levels of ferroptosis-related proteins(glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1),long-chain-fatty-acid-CoA ligase 4(ACSL4),transferrin receptor 1(TfR1))were detected by Western Blot.Results Compared with each control mice,all model mice exhibited obvious redness,swelling,scratching,desquamation,and rough thickening of the skin,and skin thickness was significantly increased(P＜0.01).ROS,IFN-γ,IL-4,and MDA levels were elevated to varying extents(P＜0.05)and histopathological features,including epidermal hyperplasia,keratinocyte degeneration,dermal vascular congestion,and immune cell infiltration,were detected in model mice.Transmission electron microscopy also revealed mitochondrial membrane rupture,increased density,and cristae reduction.Expression levels of ferroptosis markers were dysregulated,including significantly decreased GPX4/FTH1(P＜0.05)and increased ACSL4/TfR1 expression(P＜0.05).Conclusions All three chemicals successfully induced AD-like phenotypes in BALB/c mice through site-specific applications.Ferroptosis is involved in the pathological process of AD,but heterogeneity exists among inducers and modeling sites.
