HMGB1通过抑制黑色素细胞gp100诱发铁死亡并放大炎症级联促进白癜风发病OA

Objective To explore the effect of high mobility group box 1(HMGB1)on patho-genesis of vitiligo through inhibition of glycoprotein 100(gp100)and Nrf-2/HO-1/GPX4 expres-sion,promotion of ferroptosis,and amplification of the inflammatory cascade.Methods A total of 24 C57BL/6 male mice aged 5-6 weeks were randomly divided into 4 groups,with 6 mice in each group:control group,model group,model+HMGB1 treatment group and model+gp100 degrad-ing peptide treatment group.A mouse model of hydroquinone-induced vitiligo was established.The expression levels of HMGB1,gp100,the ferroptosis-related factors(GPX4,SLC7A11)and the endoplasmic reticulum stress-related factors(PERK,p-PERK,ATF6,GRP78,Nrf-2,HO-1)were detected by Western blotting.ELISA was used to measure the levels of TNF-α,IL-6 and MDA.DHE fluorescent probe was used to determine the ROS levels in mice skin tissues.Hematoxylin-eosin(HE)staining and histopathological analysis were performed in mice skin tissues.Results Compared with those in the control group,the score of depigmentation area,the levels of ROS,TNF-α,IL-6,MDA,and the expression levels of HMGB1,SLC7A11,p-PERK,ATF6 and GRP78 in the model group were increased(all P<0.01),whereas the expres-sion levels of gp100 and GPX4 were decreased(P<0.01).The epidermal cells in the model group were disorderly arranged.In the HMGB1 treatment group,the expression levels of Nrf-2,HO-1 and gp100 were decreased(P<0.05),whereas the expression levels of p-PERK,ATF6 and GRP78 were increased(P<0.05).The levels of ROS,MDA and the expression level of SLC7A11 were in-creased in the gp100 degrading peptide treatment group(P<0.05),and the epidermal cells were more loosely arranged,with a large number of melanocytes undergoing apoptosis.Conclusion HMGB1 may be involved in inhibiting gp100 expression in melanocytes by mediating endoplasmic reticulum stress and inflammatory cascades,and down-regulating Nrf-2/HO-1/GPX4 to promote fer-roptosis in melanocytes.