
浏览全部资源
扫码关注微信
1.陕西中医药大学基础医学院,咸阳 712046
2.陕西中医药大学第一临床医学院,咸阳 712046
王友霞,Email:wangyouxia56@163.com,研究方向:中医体质理论的实验及临床应用研究。
李翠娟,Email:ligong1212@sohu.com。
收稿:2025-01-16,
修回:2025-02-27,
录用:2025-03-20,
纸质出版:2025-10-28
移动端阅览
王友霞,李翠娟,巩振东,等.AQP5调控细胞程序性死亡在干燥综合征中的研究现状[J].重庆医科大学学报,2025,50(10):1385-1391.
Wang Youxia,Li Cuijuan,Gong Zhendong,et al.Current research status of aquaporin 5 in regulating programmed cell death in Sjögren’s syndrome[J].Journal of Chongqing Medical University,2025,50(10):1385-1391.
王友霞,李翠娟,巩振东,等.AQP5调控细胞程序性死亡在干燥综合征中的研究现状[J].重庆医科大学学报,2025,50(10):1385-1391. DOI: 10.13406/j.cnki.cyxb.003835.
Wang Youxia,Li Cuijuan,Gong Zhendong,et al.Current research status of aquaporin 5 in regulating programmed cell death in Sjögren’s syndrome[J].Journal of Chongqing Medical University,2025,50(10):1385-1391. DOI: 10.13406/j.cnki.cyxb.003835.
水通道蛋白5(aquaporin 5,AQP5)是一种能明显提升细胞膜水通透性,参与水的分泌、吸收过程,以及维持细胞内外水分子的平衡状态,跨膜转运水的特异性蛋白。细胞程序性死亡(programmed cell death,PCD)与干燥综合征(sjögren’s syndrome,SS)的发生发展过程有着密切的联系。AQP5可能通过调节PCD机制,进而影响SS的发生与发展。本文综述了近年来关于AQP5在PCD相关的细胞凋亡、焦亡、自噬及铁死亡等过程调控中的分子机制,同时深入探讨了其对SS可能产生的潜在影响,旨在为SS的临床预防与治疗提供理论依据。
Aquaporin 5(AQP5) is a specific protein that can significantly increase the water permeability of cell membrane,participate in the process of water secretion and absorption,maintain the balance of water molecules inside and outside the cell,and transport water across the membrane. Programmed cell death(PCD) is closely associated with the development and progression of Sjögren’s syndrome(SS). AQP5 may influence the development and progression of SS by regulating the PCD mechanism. This article reviews the molecular mechanisms of AQP5 in regulating the apoptosis,pyroptosis,autophagy,and ferroptosis of cells in recent years and discusses the potential influence of AQP5 on SS,in order to provide a theoretical basis for the clinical prevention and treatment of SS.
Parisis D , Chivasso C , Perret J , et al . Current state of knowledge on primary sjögren’s syndrome,an autoimmune exocrinopathy [J ] . J Clin Med , 2020 , 9 ( 7 ): 2299 .
Bjordal O , Norheim KB , Rødahl E , et al . Primary sjögren’s syndrome and the eye [J ] . Surv Ophthalmol , 2020 , 65 ( 2 ): 119 - 132 .
王瑞婷 , 陈雁飞 , 汪钰涵 , 等 . T细胞亚群在原发性干燥综合征发病机制中的研究进展 [J ] . 兰州大学学报(医学版) , 2020 , 46 ( 6 ): 45 - 50 .
Wang RT , Chen YF , Wang YH , et al . Advances in the study of T-cell subsets in the pathogenesis of primary sjögren’s syndrome [J ] . J Lanzhou Univ Med Sci , 2020 , 46 ( 6 ): 45 - 50 .
Vivino FB , Bunya VY , Massaro-Giordano G , et al . Sjögren’s syndrome:an update on disease pathogenesis,clinical manifestations and treatment [J ] . Clin Immunol , 2019 , 203 : 81 - 121 .
Jeon S , Lee J , Park SH , et al . Associations of anti-aquaporin 5 autoantibodies with serologic and histopathological features of sjögren’s syndrome [J ] . J Clin Med , 2019 , 8 ( 11 ): 1863 .
沙明慧 , 吴素玲 . 水通道蛋白5在干燥综合征中的作用综述 [J ] . 药学与临床研究 , 2019 , 27 ( 2 ): 113 - 116 .
Sha MH , Wu SL . Aquaporin 5 in the role of sjögren’s syndrome [J ] . Pharm Clin Res , 2019 , 27 ( 2 ): 113 - 116 .
Matsuzaki T , Susa T , Shimizu K , et al . Function of the membrane water channel aquaporin-5 in the salivary gland [J ] . Acta Histochem Cytochem , 2012 , 45 ( 5 ): 251 - 259 .
Xiao L , Ng TB , Feng YB , et al . Dendrobium candidum extract increases the expression of aquaporin-5 in labial glands from patients with sjögren’s syndrome [J ] . Phytomedicine , 2011 , 18 ( 2/3 ): 194 - 198 .
罗慧臣 , 李 萍 , 肖卫国 . M3R与AQP5在干燥综合征患者唇腺中的表达与意义 [J ] . 中国免疫学杂志 , 2011 , 27 ( 1 ): 79 - 81,87 .
Luo HC , Li P , Xiao WG . Expression of muscarinic receptor 3 and aquaporin 5 in patients with sjögren’s syndrome in the labial glands [J ] . Chin J Immunol , 2011 , 27 ( 1 ): 79 - 81,87 .
王 领 , 张 娜 , 王艳玲 , 等 . 原发性干燥综合征患者唇腺组织水通道蛋白5的表达及意义 [J ] . 上海交通大学学报(医学版) , 2020 , 40 ( 10 ): 1425 - 1429 .
Wang L , Zhang N , Wang YL , et al . Expression of aquaporin 5 in labial gland of patients with primary sjögren’s syndrome and its significance [J ] . J Shanghai Jiao Tong Univ Med Sci , 2020 , 40 ( 10 ): 1425 - 1429 .
Ma T , Song Y , Gillespie A , et al . Defective secretion of saliva in transgenic mice lacking aquaporin-5 water channels [J ] . J Biol Chem , 1999 , 274 ( 29 ): 20071 - 20074 .
肖 胤 , 罗 玲 , 杨军 , 等 . 铁皮石斛对干燥综合征患者的治疗作用及其可能机制的研究 [J ] . 检验医学与临床 , 2017 , 14 ( 23 ): 3464 - 3466 .
Xiao Y , Luo L , Yang J , et al . The effect of tin caulis dendrobii on the treatment of patients with sjögren’s syndrome and its possible mechanism [J ] . Lab Med Clin , 2017 , 14 ( 23 ): 3464 - 3466 .
任雅婷 , 刘 丹 , 周东海 , 等 . 益气养阴祛瘀方对干燥综合征NOD小鼠颌下腺AQP5、M3R表达的影响 [J ] . 中药新药与临床药理 , 2023 , 34 ( 5 ): 613 - 619 .
Ren YT , Liu D , Zhou DH , et al . Effects of Yiqi Yangyin Quyu prescription on the expressions of AQP5 and M3R in submandibular glands of NOD mice with sjögren’s syndrome [J ] . Tradit Chin Drug Res Clin Pharmacol , 2023 , 34 ( 5 ): 613 - 619 .
陈剑梅 . 津血源及其标志性单体对干燥综合征模型鼠唾液腺M 3-Ca 2+ -AQP5途径的影响 [D ] . 南京 : 南京中医药大学 , 2018 .ChenJM. Effects of Jinxueyuan and its iconic monomer on M 3
-Ca 2+ -AQP 5 pathway of salivary gland in sjögren’s syndrome model mice [D ] . Nanjing : Nanjing University of Chinese Medicine ,2018.
牛瑞娟 . 人参皂苷Rh1对IFN-γ诱导的人唾液腺细胞炎症和凋亡的抑制作用研究 [D ] . 长春 : 吉林大学 , 2022 .
Niu RJ . Inhibitory effect of ginsenoside Rh1 on IFN-γ-induced inflammation and apoptosis of human salivary gland cells [D ] . Changchun : Jilin University , 2022 .
张艺凡 , 孙明辉 . 生津汤对干燥综合征患者AQP5及炎症因子的影响 [J ] . 西部中医药 , 2024 , 37 ( 9 ): 136 - 139 .
Zhang YF , Sun MH . Influence of body fluid-generating decoction on AQP5 and inflammatory factors in patients with primary sjögren’s syndrome [J ] . West J Tradit Chin Med , 2024 , 37 ( 9 ): 136 - 139 .
Ichiyama T , Nakatani E , Tatsumi K , et al . Expression of aquaporin 3 and 5 as a potential marker for distinguishing dry mouth from sjögren’s syndrome [J ] . J Oral Sci , 2018 , 60 ( 2 ): 212 - 220 .
Chivasso C , Nesverova V , Järvå M , et al . Unraveling human AQP5-PIP molecular interaction and effect on AQP5 salivary glands localization in SS patients [J ] . Cells , 2021 , 10 ( 8 ): 2108 .
王新昌 , 曹灵勇 , 范永升 . 干燥综合征中医病因病机刍议 [J ] . 浙江中医药大学学报 , 2011 , 35 ( 5 ): 643 - 644 .
Wang XC , Cao LY , Fan YS . Discussion of the etiology and pathogenesis of traditional Chinese medicine of sjögren’s syndrome [J ] . J Zhejiang Chin Med Univ , 2011 , 35 ( 5 ): 643 - 644 .
Kopeina GS , Zhivotovsky B . Programmed cell death:Past,present and future [J ] . Biochem Biophys Res Commun , 2022 , 633 : 55 - 58 .
Bedoui S , Herold MJ , Strasser A . Emerging connectivity of programmed cell death pathways and its physiological implications [J ] . Nat Rev Mol Cell Biol , 2020 , 21 ( 11 ): 678 - 695 .
Carneiro BA , El-Deiry WS . Targeting apoptosis in cancer therapy [J ] . Nat Rev Clin Oncol , 2020 , 17 ( 7 ): 395 - 417 .
Longhino S , Chatzis LG , Dal Pozzolo R , et al . Sjögren’s syndrome:one year in review 2023 [J ] . Clin Exp Rheumatol , 2023 , 41 ( 12 ): 2343 - 2356 .
Witas R , Peck AB , Ambrus JL , et al . Sjögren’s syndrome and TAM receptors:a possible contribution to disease onset [J ] . J Immunol Res , 2019 , 2019 : 4813795 .
黄子玮 , 陶庆文 , 廖佳禾 , 等 . 化湿润燥方调控Hippo-YAP/TAZ表达对干燥综合征模型小鼠颌下腺细胞凋亡和功能的影响 [J ] . 北京中医药大学学报 , 2024 , 47 ( 11 ): 1527 - 1540 .
Huang ZW , Tao QW , Liao JH , et al . Effect of Huashi Runzao Prescription on apoptosis and function of submandibular gland in sjögren’s syndrome model mice by regulating Hippo-YAP/TAZ expression [J ] . J Beijing Chin Med Univ , 2024 , 47 ( 11 ): 1527 - 1540 .
Chivasso C , D’Agostino C , Parisis D , et al . Involvement of aquaporin 5 in sjögren’s syndrome [J ] . Autoimmun Rev , 2023 , 22 ( 3 ): 103268 .
Soyfoo MS , Chivasso C , Perret J , et al . Involvement of aquaporins in the pathogenesis,diagnosis and treatment of sjögren’s syndrome [J ] . Int J Mol Sci , 2018 , 19 ( 11 ): 3392 .
Li P , Yang Y , Jin Y , et al . B7-H3 participates in human salivary gland epithelial cells apoptosis through NF-κB pathway in primary sjögren’s syndrome [J ] . J Transl Med , 2019 , 17 ( 1 ): 268 .
汤艳春 , 王吉波 , 孙雪辉 , 等 . 原发性干燥综合征唇腺组织中细胞凋亡及相关基因表达的研究 [J ] . 中华风湿病学杂志 , 2004 , 8 ( 9 ): 522 - 525,580 .
Tang YC , Wang JB , Sun XH , et al . Apoptosis and related gene expression in minor labial salivary gland of patients with primary sjögren’s syndrome [J ] . Chin J Rheumatol , 2004 , 8 ( 9 ): 522 - 525,580 .
Miao EA , Leaf IA , Treuting PM , et al . Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria [J ] . Nat Immunol , 2010 , 11 ( 12 ): 1136 - 1142 .
王 芳 , 李开颖 , 蔡振宇 . 程序性细胞死亡与肿瘤 [J ] . 中国细胞生物学学报 , 2022 , 44 ( 4 ): 539 - 550 .
Wang F , Li KY , Cai ZY . Programmed cell death and tumor [J ] . Chin J Cell Biol , 2022 , 44 ( 4 ): 539 - 550 .
Shi JJ , Gao WQ , Shao F . Pyroptosis:gasdermin-mediated programmed necrotic cell death [J ] . Trends Biochem Sci , 2017 , 42 ( 4 ): 245 - 254 .
Hett EC , Slater LH , Mark KG , et al . Chemical genetics reveals a kinase-independent role for protein kinase R in pyroptosis [J ] . Nat Chem Biol , 2013 , 9 ( 6 ): 398 - 405 .
Cookson BT , Brennan MA . Pro-inflammatory programmed cell death [J ] . Trends Microbiol , 2001 , 9 ( 3 ): 113 - 114 .
Zhang KY , Luo ZY , Zhu XC , et al . Identification of key genes for pyroptosis-induced salivary gland inflammation in sjögren’s syndrome based on microarray data and immunohistochemistry analysis [J ] . J Inflamm Res , 2023 , 16 : 5865 - 5879 .
Wang K , Sun Q , Zhong X , et al . Structural mechanism for GSDMD targeting by autoprocessed caspases in pyroptosis [J ] . Cell , 2020 , 180 ( 5 ): 941 - 955 .
Shi JJ , Zhao Y , Wang K , et al . Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death [J ] . Nature , 2015 , 526 ( 7575 ): 660 - 665 .
Cao X , Di GH , Bai Y , et al . Aquaporin5 deficiency aggravates ROS/NLRP3 inflammasome-mediated pyroptosis in the lacrimal glands [J ] . Invest Ophthalmol Vis Sci , 2023 , 64 ( 1 ): 4 .
夏凯雨 , 李奇玮 , 李泽光 , 等 . 基于ROS/NLRP3介导的泪腺上皮细胞焦亡探讨梅花生津饮治疗干燥综合征的机制研究 [J ] . 海南医科大学学报 , 2025 , 31 ( 1 ): 33 - 40 .
Xia KY , Li QW , Li ZG , et al . Mechanism of Meihua Shengjin Decoction in the treatment of sjögren’s syndrome through ROS/NLRP3-mediated pyroptosis of lacrimal epithelial cells [J ] . J Hainan Med Univ , 2025 , 31 ( 1 ): 33 - 40 .
Zhang Z , Shao XH , Jiang N , et al . Caspase-11-mediated tubular epithelial pyroptosis underlies contrast-induced acute kidney injury [J ] . Cell Death Dis , 2018 , 9 ( 10 ): 983 .
Wu MY , Lu JH . Autophagy and macrophage functions:inflammatory response and phagocytosis [J ] . Cells , 2019 , 9 ( 1 ): 70 .
Alers S , Löffler AS , Wesselborg S , et al . Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy:cross talk,shortcuts,and feedbacks [J ] . Mol Cell Biol , 2012 , 32 ( 1 ): 2 - 11 .
Shah M , Edman MC , Janga SR , et al . A rapamycin-binding protein polymer nanoparticle shows potent therapeutic activity in suppressing autoimmune dacryoadenitis in a mouse model of sjögren’s syndrome [J ] . J Control Release , 2013 , 171 ( 3 ): 269 - 279 .
王 梦 , 刘 焰 . 雷帕霉素缓释微球治疗干燥综合征性干眼的疗效评估 [J ] . 国际眼科杂志 , 2013 , 13 ( 5 ): 861 - 864 .
Wang M , Liu Y . Effect assessment of subconjunctival injection of rapamycin-loaded microspheres in non-obese diabetic mice with dry eye caused by sjögren’s syndrome [J ] . Int Eye Sci , 2013 , 13 ( 5 ): 861 - 864 .
Kanaizumi H , Higashi C , Tanaka Y , et al . PI3K/Akt/mTOR signalling pathway activation in patients with ER-positive,metachronous,contralateral breast cancer treated with hormone therapy [J ] . Oncol Lett , 2019 , 17 ( 2 ): 1962 - 1968 .
张睿鑫 , 付 萍 . p-S6在干燥综合征患者唇腺组织中的表达 [J ] . 中国皮肤性病学杂志 , 2021 , 35 ( 12 ): 1342 - 1346 .
Zhang RX , Fu P . Expression of p-S6 in labial glands of patients with sjögren’s syndrome [J ] . Chin J Dermatovenereology , 2021 , 35 ( 12 ): 1342 - 1346 .
Cheng XL , Hu J , Liu XF , et al . Therapeutic targets by traditional Chinese medicine for ischemia-reperfusion injury induced apoptosis on cardiovascular and cerebrovascular diseases [J ] . Front Pharmacol , 2022 , 13 : 934256 .
Lennikov A , Mukwaya A , Saddala MS , et al . Deficiency of C-X-C chemokine receptor type 5(CXCR5) gene causes dysfunction of retinal pigment epithelium cells [J ] . Lab Invest , 2021 , 101 ( 2 ): 228 - 244 .
雷玲彦 , 郭惠芳 , 张明峰 , 等 . Tfh细胞在原发性干燥综合征中的致病作用 [J ] . 中国免疫学杂志 , 2014 , 30 ( 3 ): 392 - 395,399 .
Lei LY , Guo HF , Zhang MF , et al . Role of Tfh cells in pathogenesis of primary sjögren’s syndrome [J ] . Chin J Immunol , 2014 , 30 ( 3 ): 392 - 395,399 .
Zhao R , He BY , Bie QL , et al . AQP5 complements LGR5 to determine the fates of gastric cancer stem cells through regulating ULK1 ubiquitination [J ] . J Exp Clin Cancer Res , 2022 , 41 ( 1 ): 322 .
仲诗艳 . 沉默AQP5对结直肠癌细胞自噬的影响及机制研究 [D ] . 锦州 : 锦州医科大学 , 2023 .
Zhong SY . Effect of silencing AQP5 on autophagy of colorectal cancer cells and its mechanism [D ] . Jinzhou : Jinzhou Medical University , 2023 .
Liang C , Zhang XL , Yang MS , et al . Recent progress in ferroptosis inducers for cancer therapy [J ] . Adv Mater , 2019 , 31 ( 51 ): e1904197 .
Yu Y , Yan Y , Niu FL , et al . Ferroptosis:a cell death connecting oxidative stress,inflammation and cardiovascular diseases [J ] . Cell Death Discov , 2021 , 7 ( 1 ): 193 .
Li JY , Yao YM , Tian YP . Ferroptosis:a trigger of proinflammatory state progression to immunogenicity in necroinflammatory disease [J ] . Front Immunol , 2021 , 12 : 701163 .
Jimenez F , Aiba-Masago S , Al Hashimi I , et al . Activated caspase 3 and cleaved poly(ADP-ribose)polymerase in salivary epithelium suggest a pathogenetic mechanism for sjögren’s syndrome [J ] . Rheumatology(Oxford) , 2002 , 41 ( 3 ): 338 - 342 .
Lee YS , Lee DH , Choudry HA , et al . Ferroptosis-induced endoplasmic reticulum stress:cross-talk between ferroptosis and apoptosis [J ] . Mol Cancer Res , 2018 , 16 ( 7 ): 1073 - 1076 .
Ooko E , Saeed MEM , Kadioglu O , et al . Artemisinin derivatives induce iron-dependent cell death(ferroptosis) in tumor cells [J ] . Phytomedicine , 2015 , 22 ( 11 ): 1045 - 1054 .
Matsushita M , Freigang S , Schneider C , et al . T cell lipid peroxidation induces ferroptosis and prevents immunity to infection [J ] . J Exp Med , 2015 , 212 ( 4 ): 555 - 568 .
Yang Y , Wang Y , Guo L , et al . Interaction between macrophages and ferroptosis [J ] . Cell Death Dis , 2022 , 13 ( 4 ): 355 .
Shah R , Shchepinov MS , Pratt DA . Resolving the role of lipoxygenases in the initiation and execution of ferroptosis [J ] . ACS Cent Sci , 2018 , 4 ( 3 ): 387 - 396 .
Cao TT , Zhou JN , Liu QW , et al . Interferon-γ induces salivary gland epithelial cell ferroptosis in sjögren’s syndrome via JAK/STAT1-mediated inhibition of system Xc [J ] . Free Radic Biol Med , 2023 , 205 : 116 - 128 .
Zhou JN , Pathak JL , Cao TT , et al . CD4 T cell-secreted IFN-γ in sjögren’s syndrome induces salivary gland epithelial cell ferroptosis [J ] . Biochim Biophys Acta Mol Basis Dis , 2024 , 1870 ( 4 ): 167121 .
Zhou JN , Pathak JL , Wu LH , et al . Downregulated GPX4 in salivary gland epithelial cells contributes to salivary secretion dysfunction in sjögren’s syndrome via lipid ROS/pSTAT4/AQP5 axis [J ] . Free Radic Biol Med , 2024 , 218 : 1 - 15 .
Takashi Y , Tomita K , Kuwahara Y , et al . Mitochondrial dysfunction promotes aquaporin expression that controls hydrogen peroxide permeability and ferroptosis [J ] . Free Radic Biol Med , 2020 , 161 : 60 - 70 .
0
浏览量
4
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621