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

doi:10.3870/j.issn.1672-8009.2026.01.003

医学分子生物学杂志 ›› 2026, Vol. 23 ›› Issue (1): 19-26.doi: 10.3870/j.issn.1672-8009.2026.01.003

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

耿颖颖¹, 孙中斌², 黄鹏飞¹, 王云馨¹, 崔婷婷¹

¹新疆医科大学基础医学院生物化学与分子生物学教研室,中亚高发疾病机制与防治国家重点实验室,新疆地方病分子生物学重点实验室乌鲁木齐市,830017
²新疆军区总医院皮肤科乌鲁木齐市,830017

收稿日期:2025-04-18 发布日期:2026-01-29
通讯作者: 崔婷婷(E-mail:cuitt_1210@126.com)
基金资助:
新疆维吾尔自治区自然科学基金杰出青年项目(No.2022D01E52)

Effect of HMGB1 on gp100 Expression and Ferroptosis in Melanocytes and Inflammatory Cascades in Vitiligo

GENG Yingying, SUN Zhongbin, HUANG Pengfei, WANG Yunxin, CUI Tingting

¹Department of Biochemistry and Molecular Biology,School of Basic Medicine,State Key Laboratory of Pathogenesis,Prevention and Treatment of Central Asian High Incidente Diseases,Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases,Xinjiang Medical University,Urumqi,830011,China
²Department of Dermatology,General Hospital of Xinjiang Military Command,Urumqi,830000,China

Received:2025-04-18 Published:2026-01-29
Contact: CUI Tingting(E-mail:cuitt_1210@126.com)
Supported by:
Scientist Found for Distinguished Young Scholars of Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2022D01E52)

摘要/Abstract

摘要： 目的探讨高迁移率族蛋白1(high mobility group box 1,HMGB1)抑制黑色素细胞糖蛋白100(glycoprotein 100,gp100)和Nrf-2/HO-1/GPX4促进细胞铁死亡并放大炎症级联在白癜风发病中的作用及机制。方法 24只5~6周龄雄性C57BL/6小鼠随机分为4组(对照组、模型组、模型+HMGB1处理组和模型+gp100降解肽处理组),每组6只。建立对苯二酚诱导的白癜风小鼠模型。蛋白质印迹检测小鼠皮肤组织HMGB1、gp100、铁死亡相关因子GPX4和SLC7A11、内质网应激相关因子PERK、p-PERK、ATF6和GRP78,以及Nrf-2和HO-1表达水平。ELISA测定小鼠皮肤组织TNF-α、IL-6和MDA的水平。DHE荧光探针法测定小鼠皮肤组织ROS水平。对小鼠皮肤组织进行苏木精-伊红(HE)染色和组织病理学分析。结果与对照组比较,模型组小鼠皮肤脱色区域评分升高(P<0.01),ROS水平增加,TNF-α、IL-6及MDA水平升高,HMGB1、SLC7A11及内质网应激相关因子p-PERK、ATF6和GRP78表达水平升高(P<0.01),gp100和GPX4表达水平降低(P<0.01);表皮部细胞排列松散、紊乱,组织间隙增大。HMGB1处理组Nrf-2、HO-1、gp100表达降低(P<0.05),p-PERK、ATF6和GRP78表达升高(P<0.05);gp100降解肽处理组ROS水平、MDA水平和SLC7A11相对表达水平升高(P<0.05),且表皮细胞排列更为松散、黑色素细胞大量凋亡,组织间隙较大。结论 HMGB1可能通过介导内质网应激和炎症级联,参与抑制黑色素细胞gp100的表达,下调Nrf-2/HO-1/GPX4促进黑色素细胞铁死亡。

关键词: 白癜风, 黑色素细胞, 高迁移率族蛋白1, 糖蛋白100, 内质网应激, 铁死亡

Abstract: Objective To explore the effect of high mobility group box 1(HMGB1)on pathogenesis of vitiligo through inhibition of glycoprotein 100(gp100) and Nrf-2/HO-1/GPX4 expression,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 degrading 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 expression 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 increased 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 ferroptosis in melanocytes.

Key words: vitiligo, melanocyte, HMGB1, gp100, endoplasmic reticulum stress, ferroptosis

中图分类号:

R751

耿颖颖, 孙中斌, 黄鹏飞, 王云馨, 崔婷婷. 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[J]. 医学分子生物学杂志, 2026, 23(1): 19-26.

GENG Yingying, SUN Zhongbin, HUANG Pengfei, WANG Yunxin, CUI Tingting. Effect of HMGB1 on gp100 Expression and Ferroptosis in Melanocytes and Inflammatory Cascades in Vitiligo[J]. Journal of Medical Molecular Biology, 2026, 23(1): 19-26.

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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

Effect of HMGB1 on gp100 Expression and Ferroptosis in Melanocytes and Inflammatory Cascades in Vitiligo

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