铁死亡在唾液腺疾病中的研究进展

doi:10.13701/j.cnki.kqyxyj.2025.11.001

摘要/Abstract

摘要： 铁死亡(ferroptosis)是一种铁依赖性细胞程序性死亡方式,其核心特征包括铁离子介导的脂质过氧化和谷胱甘肽过氧化物酶4活性的下降。唾液腺疾病包括腮腺炎、干燥综合征、放射性唾液腺损伤及良、恶性肿瘤等,以往研究在攻克这些疾病时存在瓶颈。近年来,铁死亡在多种疾病中的作用逐渐受到关注,尤其是在唾液腺疾病中,铁死亡机制与唾液腺疾病的起始、发展及转归密切相关。本文旨在深度梳理铁死亡与唾液腺疾病的内在联系,为探索唾液腺相关疾病发病机制提供全新视角。

关键词: 铁死亡, 唾液腺疾病, 脂质过氧化, 铁代谢, 研究进展

Abstract: Ferroptosis is a form of programmed cell death that is dependent on iron and is characterized by the peroxidation of lipids mediated by iron, as well as decreased activity of glutathione peroxidase 4 (GPX4). Salivary gland diseases include conditions such as mumps, Sjögren's syndrome, radiation-induced salivary gland injury, and both benign and malignant tumors. Previous studies have faced challenges in addressing these diseases. In recent years, researchers have increasingly focused on the role of ferroptosis in various diseases, particularly in salivary gland disease. The mechanisms behind ferroptosis closely relate to the initiation, progression, and prognosis of these conditions. The purpose of this article is to explore the intrinsic relationship between ferroptosis and salivary gland diseases, providing new insights into these conditions.

Key words: ferroptosis, salivary gland disease, lipid peroxidation, iron metabolism, research progress

杨蓉, 许辉. 铁死亡在唾液腺疾病中的研究进展[J]. 口腔医学研究, 2025, 41(11): 931-936.

YANG Rong, XU Hui. Research Progress on Mechanism of Ferroptosis in Salivary Gland Disease[J]. Journal of Oral Science Research, 2025, 41(11): 931-936.

参考文献

[1] Caraba A, Roman D, Crişan V, et al. Salivary flow rate in patients with sjögren’s syndrome: correlations with salivary gland ultrasound findings and biomarkers of disease activity[J]. Int J Mol Sci, 2024, 26(1): 101.
[2] Yan B, Ai Y, Sun Q, et al. Membrane damage during ferroptosis is caused by oxidation of phospholipids catalyzed by the oxidoreductases POR and CYB5R1[J]. Mol Cell, 2021, 81(2): 355-369.e10.
[3] Cui J, Wang Y, Tian X, et al. LPCAT3 is transcriptionally regulated by YAP/ZEB/EP300 and collaborates with acsl4 and yap to determine ferroptosis sensitivity[J]. Antioxid Redox Sign, 2023, 39(7-9): 491-511.
[4] Marteau R, Ravez S, Mazhari Dorooee D, et al. Repositioning of fda-approved antifungal agents to interrogate acyl-coa synthetase long chain family member 4 (ACSL4) in ferroptosis[J]. Biochem Pharmacol, 2022, 204(6): 115239.
[5] Ingold I, Berndt C, Schmitt S, et al. Selenium utilization by GPX4 is required to prevent hydroperoxide-induced ferroptosis[J]. Cell, 2018, 172(3): 409-422.e21.
[6] Bai L, Yan F, Deng R, et al. Thioredoxin-1 rescues MPP⁺/MPTP-induced ferroptosis by increasing glutathione peroxidase 4[J]. Mol Neurobiol, 2021, 58(7): 3187-3197.
[7] Lai Y, Dong J, Wu Y, et al. Lipid peroxides mediated ferroptosis in electromagnetic pulse-induced hippocampal neuronal damage via inhibition of GSH/GPX4 axis[J]. Int J Mol Sci, 2022, 23(16): 9277.
[8] Zhang J, Chen X, Hong J, et al. Biochemistry of mammalian ferritins in the regulation of cellular iron homeostasis and oxidative responses[J]. Sci China Life Sci, 2021, 64(3): 352-362.
[9] Lee JY, Kim WK, Bae KH, et al. Lipid metabolism and ferroptosis[J]. Biology (Basel), 2021, 10(3): 1620-1631.
[10] Li X, Li Y, Xu J, et al. Terahertz wave desensitizes ferroptosis by inhibiting the binding of ferric ions to the transferrin[J]. Acs Nano, 2025, 19(7): 6876-6889.
[11] Chen J, Fu J, Zhao S, et al. Free radical and viral infection: A review from the perspective of ferroptosis[J]. Vet Sci, 2023, 10(7):456.
[12] Seok BG, Park E, Park YJ, et al. PGC1α is a key regulator of erastin-induced mitochondrial dysfunction during ferroptotic cell death[J]. BMB Rep, 2025, 58(2): 89-94.
[13] Liu S, Chen JH, Li LC, et al. Susceptibility of mitophagy-deficient tumors to ferroptosis induction by relieving the suppression of lipid peroxidation[J]. Adv Sci (Weinh), 2024, 12(6): e2412593.
[14] Cao G, Yang C, Jin Z, et al. FNDC5/irisin reduces ferroptosis and improves mitochondrial dysfunction in hypoxic cardiomyocytes by Nrf2/HO-1 axis[J]. Cell Biol Int, 2022, 46(5): 723-736.
[15] Gan L, Wang Z, Si J, et al. Protective effect of mitochondrial-targeted antioxidant MitoQ against iron ion 56Fe radiation induced brain injury in mice[J]. Toxicol Appl Pharmacol, 2018, 341: 1-7.
[16] S B, Naidu G, Sharma A, et al. Peripheral nervous system involvement in Sjogren's syndrome and its impact on quality of life[J]. Clin Exp Med, 2023, 23(2): 539-545.
[17] Yang H, Sun C, Wang X, et al. Identification of ferroptosis-related diagnostic markers in primary Sjögren's syndrome based on machine learning[J]. Med Oral Patol Oral Cir Bucal, 2024, 29(2):e203-e210.
[18] Mori T, Shimomura R, Ito T, et al. Neonatal suppurative parotitis: Case reports and literature review[J]. Pediatr Int, 2022, 64(1): e14762.
[19] Wang L, Haralambieva IH, Ovsyannikova IG, et al. Associations of adaptive immune cell subsets with measles, mumps, and rubella-specific immune response outcomes[J]. Heliyon, 2023, 9(12): e22998.
[20] Matsuoka T, Abe M, Kobayashi H. Iron metabolism and inflammatory mediators in patients with renal dysfunction[J]. Int J Mol Sci, 2024, 25(7):3745.
[21] Wang Q, Wu H, Cheng L, et al. Mumps virus induces innate immune responses in mouse ovarian granulosa cells through the activation of Toll-like receptor 2 and retinoic acid-inducible gene I[J]. Mol Cell Endocrinol, 2016, 436: 183-194.
[22] Wang C, Wang X, Song G, et al. A high-fructose diet in rats induces systemic iron deficiency and hepatic iron overload by an inflammation mechanism[J]. J Food Biochem, 2021, 45(1): e13578.
[23] 李芬,赵婕,张海溪,等.噬血细胞综合征患者的铁代谢指标、细胞因子和肝功能的相关性[J].昆明医科大学学报,2024,45(11):110-116
[24] Zhang Z, He Y, Liu H, et al. NLRP3 regulates ferroptosis via the JAK2/STAT3 pathway in asthma inflammation: Insights from in vivo and in vitro studies[J]. Int Immunopharmacol, 2024, 143(Pt 2): 113416.
[25] Tang D, Kroemer G, Kang R. Ferroptosis in immunostimulation and immunosuppression[J]. Immunol Rev, 2024, 321(1):199-210.
[26] Tang, D, Chen, X, Kang, R, et al. Ferroptosis: molecular mechanisms and health implications. Cell Res, 2020, 31(2):107-125.
[27] Fan S, Wang K, Zhang T, et al. Mechanisms and therapeutic potential of GPX4 in pain modulation[J]. Pain Ther, 2025, 14(1): 21-45.
[28] Liu Q, Mao T, Liu F, et al. Apigenin alleviates Sjögren's syndrome-induced salivary gland epithelial cell ferroptosis via ERα signaling-mediated regulation of the ATF3/SLC7A1l axis[J]. Int Immunopharmacol, 2024, 143(Pt 2): 113409.
[29] Chen B, Fan P, Song X, et al. The role and possible mechanism of the ferroptosis-related SLC7A11/GSH/GPX4 pathway in myocardial ischemia-reperfusion injury[J]. BMC Cardiovasc Disord, 2024, 24(1): 531.
[30] Lai B, Wu CH, Wu CY, et al. Ferroptosis and autoimmune diseases[J]. Front Immunol, 2022, 13(8): 916664.
[31] Chen Q, Wang J, Xiang M, et al. The potential role of ferroptosis in systemic lupus erythematosus[J]. Front Immunol, 2022, 13: 855622.
[32] Bell HN, Stockwell BR, Zou W. Ironing out the role of ferroptosis in immunity[J]. Immunity, 2024, 57(5): 941-956.
[33] Ou S, Nie X, Qiu X, et al. Deciphering the mechanisms of long non-coding RNAs in ferroptosis: insights into its clinical significance in cancer progression and immunology[J]. Cell Death Discov, 2025, 11(1): 14.
[34] De Leon-Oliva D, Boaru DL, Minaya-Bravo AM, et al. Improving understanding of ferroptosis: Molecular mechanisms, connection with cellular senescence and implications for aging[J]. Heliyon, 2024, 10(21): e39684.
[35] Kim JM, Kim DH, Kim WT, et al. Amifostine and melatonin prevent acute salivary gland dysfunction 10 days after radiation through anti-ferroptosis and anti-ferritinophagy effects[J]. Int J Mol Sci, 2024, 25(21): 3390.
[36] Ge L, Chen W, Wei F. Annexin A1 protects epidermal stem cells against ultraviolet-B irradiation-induced mitochondrial dysfunction[J]. Arch Dermatol Res, 2024, 316(7): 385.
[37] Viswanathan V, Cao H, Saiki J, et al. Aldehyde dehydrogenase 3A1 deficiency leads to mitochondrial dysfunction and impacts salivary gland stem cell phenotype[J]. Pans Nexus, 2022, 1(2): pgac056.
[38] Lygeros S, Tsapardoni F, Mastronikolis S, et al. Pleomorphic adenoma of the maxillary sinus with orbital extension presenting with exophthalmos: a case report[J]. AME Case Rep, 2021, 5: 39.
[39] Hasegawa K, Sukegawa S, Ono S, et al. Endoscopic-assisted resection of pleomorphic adenoma in the accessory parotid gland[J]. J Med Investig, 2021, 68(3.4): 376-380.
[40] Li J, Li Y, Wang D, et al. PLAG1 interacts with GPX4 to conquer vulnerability to sorafenib induced ferroptosis through a PVT1/miR-195-5p axis-dependent manner in hepatocellular carcinoma[J]. J Exp Clin Cancer Res, 2024, 43(1): 143.
[41] Huang QT, Hu QQ, Wen ZF, et al. Iron oxide nanoparticles inhibit tumor growth by ferroptosis in diffuse large B-cell lymphoma[J]. Am J Cancer Res, 2023, 13(2): 498-508.
[42] Zhu Y, Hou H, Li Y, et al. Hyperoxia exposure induces ferroptosis and apoptosis by downregulating PLAGL2 and repressing HIF-1α/VEGF signaling pathway in newborn alveolar typeⅡ epithelial cell[J]. Redox Rep, 2024, 29(1): 2387465.
[43] Song K, Liu X, Xu H, et al. Cr(Ⅵ) induces ferroptosis in DF-1 cells by simultaneously perturbing iron homeostasis of ferritinophagy and mitophagy[J]. Sci Total Environ, 2024, 925: 171818.
[44] Jiang Y, Glandorff C, Sun M. GSH and ferroptosis: side-by-side partners in the fight against tumors[J]. Antioxidants (Basel), 2024, 13(6): 697.
[45] Zhou Q, Meng Y, Li D, et al. Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies[J]. Signal Transduct Target Ther, 2024, 9(1):55.
[46] Candelaria PV, Leoh LS, Penichet ML, et al. Antibodies targeting the transferrin receptor 1 (TfR1) as direct anti-cancer agents[J]. Front Immunol, 2021, 12: 607692.
[47] Chang PH, Akbel T, Li WW. Expression of mTOR mRNA and Tfr1 mRNA in mucoepidermoid carcinoma of parotid gland and their relationship with prognosis[J]. Shanghai Kou Qiang Yi Xue, 2019, 28(5): 499-503.
[48] Martinez EF, de Araújo VC, Navarini NF, et al. Microvesicles derived from squamous cell carcinoma induce cell death, autophagy, and invasion of benign myoepithelial cells[J]. J Oral Pathol Med, 2020, 49(8): 761-770.
[49] Hou CX, Sun NN, Han W, et al. Exosomal microRNA-23b-3p promotes tumor angiogenesis and metastasis by targeting PTEN in salivary adenoid cystic carcinoma[J]. Carcinogenesis, 2022, 43(7): 682-692.
[50] Tang Z, Jiang S, Tang W, et al. H₂O₂ self-supplying and GSH-depleting nanocatalyst for copper metabolism-based synergistic chemodynamical therapy and chemotherapy[J]. Mol Pharmaceut, 2023, 20(3): 1717-1728.