铁死亡在常见皮肤病中的研究进展

doi:10.35541/cjd.20220783

中华皮肤科杂志 ›› 2024, e20220783.doi: 10.35541/cjd.20220783

铁死亡在常见皮肤病中的研究进展

刘绿野¹,张峻岭²

¹天津中医药大学研究生院，天津 300000；²天津市中医药研究院附属医院皮肤科，天津 300000

收稿日期:2022-11-07 修回日期:2024-04-23 发布日期:2024-08-22
通讯作者: 张峻岭 E-mail:13920301679@126.com

Ferroptosis in common skin diseases

Liu Lyuye¹, Zhang Junling²

¹Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China; ²Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300000, China

Received:2022-11-07 Revised:2024-04-23 Published:2024-08-22
Contact: Zhang Junling E-mail:13920301679@126.com

摘要/Abstract

摘要： 【摘要】铁死亡是一种铁依赖性的新型细胞死亡方式，主要由谷胱甘肽过氧化物酶4的生物活性下降、脂质过氧化及活性氧的过度累积引起，涉及诸多精细复杂的调控机制，包括铁代谢、脂质代谢、氨基酸代谢及氧化/抗氧化系统。近年，有研究显示铁死亡参与部分常见皮肤疾病的发生发展。本文综述铁死亡的作用机制及其在常见皮肤疾病中的研究进展，以期为皮肤病治疗带来新的研究方向和思路。

关键词: 细胞死亡, 皮肤疾病, 铁死亡, 谷胱甘肽过氧化物酶4, 白癜风, 银屑病, 黑色素瘤, 红斑狼疮, 系统性

Abstract: 【Abstract】 Ferroptosis is a new type of iron-dependent cell death, which is mainly caused by the decreased bioactivity of glutathione peroxidase 4, lipid peroxidation, and excessive accumulation of reactive oxygen species. It involves many fine and complex regulatory mechanisms, including iron metabolism, lipid metabolism, amino acid metabolism, and oxidation/antioxidant system. In recent years, studies have shown that ferroptosis is involved in the occurrence and development of some common skin diseases. This review summarizes research progress in the role and mechanisms of action of ferroptosis in common skin diseases, aiming to bring new research directions and ideas for the treatment of skin diseases.

Key words: Cell death, Skin diseases, Ferroptosis, Glutathione peroxidase 4, Vitiligo, Psoriasis, Melanoma, Lupus erythematosus, systemic

刘绿野张峻岭. 铁死亡在常见皮肤病中的研究进展[J]. 中华皮肤科杂志, 2024,e20220783. doi:10.35541/cjd.20220783

Liu Lyuye, Zhang Junling. Ferroptosis in common skin diseases[J]. Chinese Journal of Dermatology,2024,e20220783. doi:10.35541/cjd.20220783

参考文献 43

［1］	Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron⁃dependent form of nonapoptotic cell death［J］. Cell, 2012,149（5）:1060⁃1072. doi: 10.1016/j.cell.2012.03.042.
［2］	陈丽华, 向阳. 铁死亡在肿瘤免疫治疗的研究进展［J］. 肿瘤预防与治疗, 2022,35（8）:765⁃769. doi: 10.3969/j.issn.1674⁃0904.2022.08.014.
［3］	Chen X, Comish PB, Tang D, et al. Characteristics and biomarkers of ferroptosis［J］. Front Cell Dev Biol, 2021,9:637162. doi: 10.3389/fcell.2021.637162.
［4］	Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease［J］. Nat Rev Mol Cell Biol, 2021,22（4）:266⁃282. doi: 10.1038/s41580⁃020⁃00324⁃8.
［5］	Nagasaki T, Schuyler AJ, Zhao J, et al. 15LO1 dictates glutathione redox changes in asthmatic airway epithelium to worsen type 2 inflammation［J］. J Clin Invest, 2022,132（1）:e151685. doi: 10.1172/JCI151685.
［6］	Lei G, Zhuang L, Gan B. Targeting ferroptosis as a vulnerability in cancer［J］. Nat Rev Cancer, 2022,22（7）:381⁃396. doi: 10. 1038/s41568⁃022⁃00459⁃0.
［7］	Li J, Cao F, Yin HL, et al. Ferroptosis: past, present and future［J］. Cell Death Dis, 2020,11（2）:88. doi: 10.1038/s41419⁃020⁃2298⁃2.
［8］	Lei G, Zhang Y, Hong T, et al. Ferroptosis as a mechanism to mediate p53 function in tumor radiosensitivity［J］. Oncogene, 2021,40（20）:3533⁃3547. doi: 10.1038/s41388⁃021⁃01790⁃w.
［9］	Chu B, Kon N, Chen D, et al. ALOX12 is required for p53⁃mediated tumour suppression through a distinct ferroptosis pathway［J］. Nat Cell Biol, 2019,21（5）:579⁃591. doi: 10.1038/s41556⁃019⁃0305⁃6.
［10］	Ji H, Wang W, Li X, et al. p53: a double⁃edged sword in tumor ferroptosis［J］. Pharmacol Res, 2022,177:106013. doi: 10.1016/j.phrs.2021.106013.
［11］	Wang Y, Zhao Y, Ye T, et al. Ferroptosis signaling and regulators in atherosclerosis［J］. Front Cell Dev Biol, 2021,9:809457. doi: 10.3389/fcell.2021.809457.
［12］	Dodson M, Castro⁃Portuguez R, Zhang DD. NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis［J］. Redox Biol, 2019,23:101107. doi: 10.1016/j.redox.2019.101107.
［13］	Zhao Y, Lu J, Mao A, et al. Autophagy inhibition plays a protective role in ferroptosis induced by Alcohol via the p62⁃Keap1⁃Nrf2 pathway［J］. J Agric Food Chem, 2021,69（33）:9671⁃9683. doi: 10.1021/acs.jafc.1c03751.
［14］	Chen J, Li X, Ge C, et al. The multifaceted role of ferroptosis in liver disease［J］. Cell Death Differ, 2022,29（3）:467⁃480. doi: 10.1038/s41418⁃022⁃00941⁃0.
［15］	Doll S, Freitas FP, Shah R, et al. FSP1 is a glutathione⁃independent ferroptosis suppressor［J］. Nature, 2019,575（7784）:693⁃698. doi: 10.1038/s41586⁃019⁃1707⁃0.
［16］	Bersuker K, Hendricks JM, Li Z, et al. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis［J］. Nature, 2019,575（7784）:688⁃692. doi: 10.1038/s41586⁃019⁃1705⁃2.
［17］	Wang W, Green M, Choi JE, et al. CD8（+） T cells regulate tumour ferroptosis during cancer immunotherapy［J］. Nature, 2019,569（7755）:270⁃274. doi: 10.1038/s41586⁃019⁃1170⁃y.
［18］	Wu J, Minikes AM, Gao M, et al. Intercellular interaction dictates cancer cell ferroptosis via NF2⁃YAP signalling［J］. Nature, 2019,572（7769）:402⁃406. doi: 10.1038/s41586⁃019⁃1426⁃6.
［19］	Lee H, Zandkarimi F, Zhang Y, et al. Energy⁃stress⁃mediated AMPK activation inhibits ferroptosis［J］. Nat Cell Biol, 2020,22（2）:225⁃234. doi: 10.1038/s41556⁃020⁃0461⁃8.
［20］	李春英, 李舒丽. 白癜风发病机制研究热点解析［J］. 中华皮肤科杂志, 2019,52（9）:593⁃597. doi: 10.3760/cma.j.issn.0412⁃4030.2019.09.001.
［21］	Xuan Y, Yang Y, Xiang L, et al. The role of oxidative stress in the pathogenesis of vitiligo: a culprit for melanocyte death［J］. Oxid Med Cell Longev, 2022,2022:8498472. doi: 10.1155/2022/8498472.
［22］	Villalpando⁃Rodriguez GE, Blankstein AR, Konzelman C, et al. Lysosomal destabilizing drug siramesine and the dual tyrosine kinase inhibitor lapatinib induce a synergistic ferroptosis through reduced heme oxygenase⁃1 （HO⁃1） levels［J］. Oxid Med Cell Longev, 2019,2019:9561281. doi: 10.1155/2019/9561281.
［23］	Pelle E, Huang X, Zhang Q, et al. Increased endogenous DNA oxidation correlates to increased iron levels in melanocytes relative to keratinocytes［J］. J Cosmet Sci, 2014,65（5）:277⁃284.
［24］	Wu X, Jin S, Yang Y, et al. Altered expression of ferroptosis markers and iron metabolism reveals a potential role of ferroptosis in vitiligo［J］. Pigment Cell Melanoma Res, 2022,35（3）:328⁃341. doi: 10.1111/pcmr.13032.
［25］	Orlik C, Deibel D, Küblbeck J, et al. Keratinocytes costimulate naive human T cells via CD2: a potential target to prevent the development of proinflammatory Th1 cells in the skin［J］. Cell Mol Immunol, 2020,17（4）:380⁃394. doi: 10.1038/s41423⁃019⁃0261⁃x.
［26］	Shou Y, Yang L, Yang Y, et al. Inhibition of keratinocyte ferroptosis suppresses psoriatic inflammation［J］. Cell Death Dis, 2021,12（11）:1009. doi: 10.1038/s41419⁃021⁃04284⁃5.
［27］	Rashmi R, Yuti AM, Basavaraj KH. Enhanced ferritin/iron ratio in psoriasis［J］. Indian J Med Res, 2012,135（5）:662⁃665.
［28］	Shahidi⁃Dadras M, Namazi N, Younespour S. Comparative analysis of serum copper, iron, ceruloplasmin, and transferrin levels in mild and severe psoriasis vulgaris in iranian patients［J］. Indian Dermatol Online J, 2017,8（4）:250⁃253. doi: 10. 4103/idoj.IDOJ_230_16.
［29］	Ahmed B, Qadir MI, Ghafoor S. Malignant melanoma: skin cancer⁃diagnosis, prevention, and treatment［J］. Crit Rev Eukaryot Gene Expr, 2020,30（4）:291⁃297. doi: 10.1615/Crit RevEukaryotGeneExpr.2020028454.
［30］	Wang Z, Jin D, Ma D, et al. Ferroptosis suppressed the growth of melanoma that may be related to DNA damage［J］. Dermatol Ther, 2019,32（4）:e12921. doi: 10.1111/dth.12921.
［31］	Hartman ML. Non⁃apoptotic cell death signaling pathways in melanoma［J］. Int J Mol Sci, 2020,21（8）:2980. doi: 10.3390/ijms21082980.
［32］	Tsoi J, Robert L, Paraiso K, et al. Multi⁃stage differentiation defines melanoma subtypes with differential vulnerability to drug⁃induced iron⁃dependent oxidative stress［J］. Cancer Cell, 2018,33（5）:890⁃904. doi: 10.1016/j.ccell.2018.03.017.
［33］	Viswanathan VS, Ryan MJ, Dhruv HD, et al. Dependency of a therapy⁃resistant state of cancer cells on a lipid peroxidase pathway［J］. Nature, 2017,547（7664）:453⁃457. doi: 10.1038/nature23007.
［34］	Hangauer MJ, Viswanathan VS, Ryan MJ, et al. Drug⁃tolerant persister cancer cells are vulnerable to GPX4 inhibition［J］. Nature, 2017,551（7679）:247⁃250. doi: 10.1038/nature24297.
［35］	Luo M, Wu L, Zhang K, et al. miR⁃137 regulates ferroptosis by targeting glutamine transporter SLC1A5 in melanoma［J］. Cell Death Differ, 2018,25（8）:1457⁃1472. doi: 10.1038/s41418⁃017⁃0053⁃8.
［36］	Zhang K, Wu L, Zhang P, et al. miR⁃9 regulates ferroptosis by targeting glutamic⁃oxaloacetic transaminase GOT1 in melanoma［J］. Mol Carcinog, 2018,57（11）:1566⁃1576. doi: 10.1002/mc. 22878.
［37］	Ubellacker JM, Tasdogan A, Ramesh V, et al. Lymph protects metastasizing melanoma cells from ferroptosis［J］. Nature, 2020,585（7823）:113⁃118. doi: 10.1038/s41586⁃020⁃2623⁃z.
［38］	Chen Q, Wang J, Xiang M, et al. The potential role of ferroptosis in systemic lupus erythematosus［J］. Front Immunol, 2022,13:855622. doi: 10.3389/fimmu.2022.855622.
［39］	Li P, Jiang M, Li K, et al. Glutathione peroxidase 4⁃regulated neutrophil ferroptosis induces systemic autoimmunity［J］. Nat Immunol, 2021,22（9）:1107⁃1117. doi: 10.1038/s41590⁃021⁃00993⁃3.
［40］	Wen Q, Liu J, Kang R, et al. The release and activity of HMGB1 in ferroptosis［J］. Biochem Biophys Res Commun, 2019,510（2）:278⁃283. doi: 10.1016/j.bbrc.2019.01.090.
［41］	Vats K, Kruglov O, Mizes A, et al. Keratinocyte death by ferroptosis initiates skin inflammation after UVB exposure［J］. Redox Biol, 2021,47:102143. doi: 10.1016/j.redox.2021.102143.
［42］	Liu T, Son M, Diamond B. HMGB1 in systemic lupus erythematosus［J］. Front Immunol, 2020,11:1057. doi: 10.3389/fimmu.2020.01057.
［43］	Ni S, Yuan Y, Kuang Y, et al. Iron metabolism and immune regulation［J］. Front Immunol, 2022,13:816282. doi: 10.3389/fimmu.2022.816282.

[1]	中国康复医学会皮肤病康复专业委员会中国康复医学会光动力治疗与康复专业委员会中华医学会皮肤性病学分会光动力治疗协作组. [开放获取] 氨基酮戊酸光动力疗法治疗非黑色素瘤皮肤癌临床应用专家共识（2025版）[J]. 中华皮肤科杂志, 2025, 58(1): 9-19.
[2]	吴曹英杨永婷王春申耀元贾卉卉李婷婷赵娟康晓静. 老年黑色素瘤临床病理特征及预后分析[J]. 中华皮肤科杂志, 2025, 58(1): 40-46.
[3]	金兰邱云王唯嘉康晓静丁媛. [开放获取] 生物制剂治疗老年中重度银屑病124例的临床疗效和安全性回顾分析[J]. 中华皮肤科杂志, 2025, 58(1): 47-52.
[4]	王博郑捷. 老年银屑病和特应性皮炎患者生物制剂及小分子药物治疗中应注意的问题[J]. 中华皮肤科杂志, 2025, 58(1): 72-75.
[5]	艾芳婷孙紫君苗国英姚春霞. 钙敏感受体在老年皮肤病理生理中的作用研究进展[J]. 中华皮肤科杂志, 2025, 58(1): 76-79.
[6]	陈嘉琪张禁唐隽. 新型冠状病毒感染与银屑病之间关系的研究进展[J]. 中华皮肤科杂志, 2025, 58(1): 84-88.
[7]	张嘉琪吴凡韩雨晴刘琦盘瑶. 多光子显微镜在皮肤科中的应用[J]. 中华皮肤科杂志, 2024, 57(9): 857-862.
[8]	郝峰刘国艳. [开放获取] 光学相干断层扫描技术在皮肤科的应用进展[J]. 中华皮肤科杂志, 2024, 57(9): 853-857.
[9]	王瑞霞曲岩磊艾文锦闫琳曲才杰史同新. 非大疱性嗜中性红斑狼疮1例[J]. 中华皮肤科杂志, 2024, 57(9): 832-834.
[10]	邹先彪陈锦纯曾悦郝轶. [开放获取] 超声检查在皮肤科的应用前景[J]. 中华皮肤科杂志, 2024, 57(9): 785-790.
[11]	曾悦邵惠红林诗雯温柔邹先彪. 可穿戴远程会诊设备在常见皮肤病诊断中的应用[J]. 中华皮肤科杂志, 2024, 57(9): 797-800.
[12]	乔嘉熙夏萍陈柳青. 司库奇尤单抗治疗前后银屑病局部皮损皮肤镜和反射式共聚焦显微镜特征分析[J]. 中华皮肤科杂志, 2024, 57(9): 825-829.
[13]	窦进法王建波张帅李建国刘鸿伟张守民. 新型冠状病毒感染疫情期间接受生物制剂治疗的中重度斑块状银屑病患者病情变化及影响因素分析：单中心横断面研究[J]. 中华皮肤科杂志, 2024, 57(8): 739-742.
[14]	林子沅庞天怡武静文靳慧. 多环芳烃在炎症性皮肤病发生发展中的作用研究进展[J]. 中华皮肤科杂志, 2024, 57(8): 765-769.
[15]	张亚美刘国豪陶玥包军. 内质网应激介导的 JNK/c-Jun信号通路在雷公藤内酯醇诱导小鼠体内黑色素瘤A375细胞凋亡中的作用研究[J]. 中华皮肤科杂志, 2024, 57(8): 709-714.

铁死亡在常见皮肤病中的研究进展

Ferroptosis in common skin diseases

PDF

PDF (Mobile)

可视化

摘要/Abstract

引用本文

使用本文

参考文献 43

相关文章 15

Metrics

本文评价

推荐阅读 10