1.河南中医药大学骨伤学院 河南 郑州 450046
2.河南中医药大学第二附属医院/河南省中医院骨伤病诊疗中心 河南 郑州 450002
3.河南中医药大学第一附属医院风湿免疫科 河南 郑州 450014
刘光华,男,2000—,医学硕士生,主要从事风湿骨病的发病机制及中医药治疗研究,E⁃mail:l17839954211@163.com
史栋梁,男,1974—,副教授,副主任医师,硕士生导师,主要从事风湿骨病的发病机制及中医药治疗的研究,E⁃mail:shidongliang2000@163.com
收稿:2024-06-15,
纸质出版:2025-09-26
移动端阅览
刘光华,史栋梁,王子华等.类风湿关节炎中滑膜成纤维细胞铁死亡的分子机制研究进展[J].武汉大学学报(医学版),2025,46(09):1211-1217.
LIU Guanghua,SHI Dongliang,WANG Zihua,et al.Research advances on the mechanism of ferroptosis in synovial fibroblasts in rheumatoid arthritis[J].Medical Journal of Wuhan University,2025,46(09):1211-1217.
刘光华,史栋梁,王子华等.类风湿关节炎中滑膜成纤维细胞铁死亡的分子机制研究进展[J].武汉大学学报(医学版),2025,46(09):1211-1217. DOI: 10.14188/j.1671-8852.2024.0453.
LIU Guanghua,SHI Dongliang,WANG Zihua,et al.Research advances on the mechanism of ferroptosis in synovial fibroblasts in rheumatoid arthritis[J].Medical Journal of Wuhan University,2025,46(09):1211-1217. DOI: 10.14188/j.1671-8852.2024.0453.
铁死亡是一种以铁离子依赖和脂质过氧化物积累为主要特征的新型调节性细胞死亡。在类风湿关节炎(RA)疾病进程中,滑膜成纤维细胞在具有铁死亡典型特征的铁过载和氧化应激的滑膜微环境中却能大量活化增殖,侵袭骨和软骨并造成关节畸形和功能丧失,从而加剧类风湿关节炎的病程。近年来相关研究表明类风湿关节炎的滑膜微环境中存在保护滑膜成纤维细胞免于铁死亡的独特机制,本文将综述类风湿关节炎中滑膜成纤维细胞铁死亡相关的分子作用机制,以期为类风湿关节炎的治疗提供新策略。
Ferroptosis
a novel form of regulated cell death
is characterized by its dependence on iron ions and the accumulation of lipid peroxides. In rheumatoid arthritis (RA)
synovial fibroblasts inhabit an environment marked by iron overload and oxidative stress⁃two primary hallmarks of ferroptosis. Paradoxically
these fibroblasts demonstrate increased activation and proliferation
facilitating their invasion into bone and cartilage
which culminates in joint deformities
functional impairment
and exacerbation of RA symptoms. Recent studies have identified a unique mechanism within the synovial microenvironment of RA that protects synovial fibroblasts from undergoing ferroptosis. This review critically evaluates the mechanisms associated with ferroptosis in synovial fibroblasts within the context of rheumatoid arthritis
aiming to advance novel therapeutic approaches for RA management.
SMITH M H , BERMAN J R . What is rheumatoid arthritis? [J ] . JAMA , 2022 , 327 ( 12 ): 1194 .
MAEDA K , YOSHIDA K , NISHIZAWA T , et al . Inflammation and bone metabolism in rheumatoid arthritis: Molecular mechanisms of joint destruction and pharmacological treatments [J ] . Int J Mol Sci , 2022 , 23 ( 5 ): 2871 .
ALETAHA D , SMOLEN J S . Diagnosis and management of rheumatoid arthritis: A review [J ] . JAMA , 2018 , 320 ( 13 ): 1360 ⁃ 1372 .
HONG J E , LEE C G , HWANG S , et al . Pulsed electromagnetic field (PEMF) treatment ameliorates murine model of collagen⁃induced arthritis [J ] . Int J Mol Sci , 2023 , 24 ( 2 ): 1137 .
BROCK J , BASU N , SCHLACHETZKI J C M , et al . Immune mechanisms of depression in rheumatoid arthritis [J ] . Nat Rev Rheumatol , 2023 , 19 ( 12 ): 790 ⁃ 804 .
GU J J , SU C Y , HUANG F , et al . Past, present and future: The relationship between circular RNA and immunity [J ] . Front Immunol , 2022 , 13 : 894707 .
LIN L , ZHU S L , HUANG H Y , et al . Chemically modified small interfering RNA targeting Hedgehog signaling pathway for rheumatoid arthritis therapy [J ] . Mol Ther Nucleic Acids , 2022 , 31 : 88 ⁃ 104 .
NYGAARD G , FIRESTEIN G S . Restoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast⁃like synoviocytes [J ] . Nat Rev Rheumatol , 2020 , 16 ( 6 ): 316 ⁃ 333 .
DIXON S J , LEMBERG K M , LAMPRECHT M R , et al . Ferroptosis: An iron⁃dependent form of nonapoptotic cell death [J ] . Cell , 2012 , 149 ( 5 ): 1060 ⁃ 1072 .
PHULL A R , NASIR B , HAQ I U , et al . Oxidative stress, consequences and ROS mediated cellular signaling in rheumatoid arthritis [J ] . Chem Biol Interact , 2018 , 281 : 121 ⁃ 136 .
BUSTAMANTE M F , GARCIA⁃CARBONELL R , WHISENANT K D , et al . Fibroblast⁃like synoviocyte metabolism in the pathogenesis of rheumatoid arthritis [J ] . Arthritis Res Ther , 2017 , 19 ( 1 ): 110 .
XIE Y , HOU W , SONG X , et al . Ferroptosis: Process and function [J ] . Cell Death Differ , 2016 , 23 ( 3 ): 369 ⁃ 379 .
LEI G , ZHUANG L , GAN B Y . Targeting ferroptosis as a vulnerability in cancer [J ] . Nat Rev Cancer , 2022 , 22 ( 7 ): 381 ⁃ 396 .
JIANG X J , STOCKWELL B R , CONRAD M . Ferroptosis: Mechanisms, biology and role in disease [J ] . Nat Rev Mol Cell Biol , 2021 , 22 ( 4 ): 266 ⁃ 282 .
MISHCHENKO T , BALALAEVA I , GOROKHOVA A , et al . Which cell death modality wins the contest for photodynamic therapy of cancer? [J ] . Cell Death Dis , 2022 , 13 ( 5 ): 455 .
GE C , ZHANG S , MU H , et al . Emerging mechanisms and disease implications of ferroptosis: Potential applications of natural products [J ] . Front Cell Dev Biol , 2021 , 9 : 774957 .
SHEN L , WANG X H , ZHAI C L , et al . Ferroptosis: A potential therapeutic target in autoimmune disease (Review) [J ] . Exp Ther Med , 2023 , 26 ( 2 ): 368 .
ZHAO T , YANG Q , XI Y , et al . Ferroptosis in rheumatoid arthritis: A potential therapeutic strategy [J ] . Front Immunol , 2022 , 13 : 779585 .
CHANG S , TANG M , ZHANG B , et al . Ferroptosis in inflammatory arthritis: A promising future [J ] . Front Immunol , 2022 , 13 : 955069 .
VAN SWELM R P L , WETZELS J F M , SWINKELS D W . The multifaceted role of iron in renal health and disease [J ] . Nat Rev Nephrol , 2020 , 16 ( 2 ): 77 ⁃ 98 .
TANG D L , CHEN X , KANG R , et al . Ferroptosis: Molecular mechanisms and health implications [J ] . Cell Res , 2021 , 31 ( 2 ): 107 ⁃ 125 .
BEHL T , MADAAN P , SEHGAL A , et al . Mechanistic insights expatiating the redox⁃active⁃metal⁃mediated neuronal degeneration in Parkinson's disease [J ] . Int J Mol Sci , 2022 , 23 ( 2 ): 678 .
GUO S S , CHEN Y X , XUE X F , et al . TRIB2 desensitizes ferroptosis via βTrCP⁃mediated TFRC ubiquitiantion in liver cancer cells [J ] . Cell Death Discov , 2021 , 7 ( 1 ): 196 .
WARD R J , DEXTER D T , CRICHTON R R . Iron, neuroinflammation and neurodegeneration [J ] . Int J Mol Sci , 2022 , 23 ( 13 ): 7267 .
KHORSANDI K , ESFAHANI H , GHAMSARI S K , et al . Targeting ferroptosis in melanoma: Cancer therapeutics [J ] . Cell Commun Signal , 2023 , 21 ( 1 ): 337 .
MA S , HENSON E S , CHEN Y , et al . Ferroptosis is induced following siramesine and lapatinib treatment of breast cancer cells [J ] . Cell Death Dis , 2016 , 7 ( 7 ): e2307 .
LEISCHNER C , MARONGIU L , PIOTROWSKY A , et al . Relevant membrane transport proteins as possible gatekeepers for effective pharmacological ascorbate treatment in cancer [J ] . Antioxidants , 2023 , 12 ( 4 ): 916 .
LI J Y , LIU S Q , YAO R Q , et al . A novel insight into the fate of cardiomyocytes in ischemia⁃reperfusion injury: From iron metabolism to ferroptosis [J ] . Front Cell Dev Biol , 2021 , 9 : 799499 .
YANG W S , SRIRAMARATNAM R , WELSCH M E , et al . Regulation of ferroptotic cancer cell death by GPX4 [J ] . Cell , 2014 ,156( 1 ⁃ 2 ): 317 ⁃ 331 .
WU Y , LI Y , LV G , et al . Redox dyshomeostasis strategy for tumor therapy based on nanomaterials chemistry [J ] . Chem Sci , 2022 , 13 ( 8 ): 2202 ⁃ 2217 .
CHEN X , KANG R , KROEMER G , et al . Ferroptosis in infection, inflammation, and immunity [J ] . J Exp Med , 2021 , 218 ( 6 ): e20210518 .
XING N , DU Q Y , GUO S , et al . Ferroptosis in lung cancer: A novel pathway regulating cell death and a promising target for drug therapy [J ] . Cell Death Discov , 2023 , 9 ( 1 ): 110 .
MAO C , LIU X G , ZHANG Y L , et al . DHODH⁃mediated ferroptosis defence is a targetable vulnerability in cancer [J ] . Nature , 2021 , 593 ( 7860 ): 586 ⁃ 590 .
KRAFT V A N , BEZJIAN C T , PFEIFFER S , et al . GTP cyclohydrolase 1/tetrahydrobiopterin counteract ferroptosis through lipid remodeling [J ] . ACS Cent Sci , 2020 , 6 ( 1 ): 41 ⁃ 53 .
YANG W S , STOCKWELL B R . Ferroptosis: Death by lipid peroxidation [J ] . Trends Cell Biol , 2016 , 26 ( 3 ): 165 ⁃ 176 .
CHENG C F , LIAO H J , WU C S . Tissue microenvironment dictates inflammation and disease activity in rheumatoid arthritis [J ] . J Formos Med Assoc , 2022 , 121 ( 6 ): 1027 ⁃ 1033 .
CROFT A P , CAMPOS J , JANSEN K , et al . Distinct fibroblast subsets drive inflammation and damage in arthritis [J ] . Nature , 2019 , 570 ( 7760 ): 246 ⁃ 251 .
WU J , FENG Z , CHEN L , et al . TNF antagonist sensitizes synovial fibroblasts to ferroptotic cell death in collagen⁃induced arthritis mouse models [J ] . Nat Commun , 2022 , 13 ( 1 ): 676 .
ANSARI M A , NADEEM A , ATTIA S M , et al . Rituximab exerts its anti⁃arthritic effects via inhibiting NF⁃κB/GM⁃CSF/iNOS signaling in B cells in a mouse model of collagen⁃induced arthritis [J ] . Heliyon , 2023 , 9 ( 6 ): e16673 .
TAK P P , FIRESTEIN G S . NF⁃kappaB: A key role in inflammatory diseases [J ] . J Clin Invest , 2001 , 107 ( 1 ): 7 ⁃ 11 .
XIAO C P , LV C , SUN S Y , et al . TSP1 is the essential domain of SEMA5A involved in pannus formation in rheumatoid arthritis [J ] . Rheumatology , 2021 , 60 ( 12 ): 5833 ⁃ 5842 .
PAN G Q , ZHU Z , HUANG J , et al . Semaphorin 5A promotes gastric cancer invasion/metastasis via urokinase⁃type plasminogen activator/phosphoinositide 3⁃kinase/protein kinase B [J ] . Dig Dis Sci , 2013 , 58 ( 8 ): 2197 ⁃ 2204 .
CHENG Q , CHEN M , LIU M , et al . Semaphorin 5A suppresses ferroptosis through activation of PI3K⁃AKT⁃mTOR signaling in rheumatoid arthritis [J ] . Cell Death Dis , 2022 , 13 ( 7 ): 608 .
DUCKER G S , RABINOWITZ J D . One⁃carbon metabolism in health and disease [J ] . Cell Metab , 2017 , 25 ( 1 ): 27 ⁃ 42 .
YANG X Y , ZHENG K D , LIN K , et al . Energy metabolism disorder as a contributing factor of rheumatoid arthritis: A comparative proteomic and metabolomic study [J ] . PLoS One , 2015 , 10 ( 7 ): e0132695 .
NÉMETH T , NAGY G , PAP T . Synovial fibroblasts as potential drug targets in rheumatoid arthritis, where do we stand and where shall we go? [J ] . Ann Rheum Dis , 2022 , 81 ( 8 ): 1055 ⁃ 1064 .
LING H Z , LI M , YANG C L , et al . Glycine increased ferroptosis via SAM⁃mediated GPX4 promoter methylation in rheumatoid arthritis [J ] . Rheumatology , 2022 , 61 ( 11 ): 4521 ⁃ 4534 .
TERZI E M , SVIDERSKIY V O , ALVAREZ S W , et al . Iron⁃sulfur cluster deficiency can be sensed by IRP2 and regulates iron homeostasis and sensitivity to ferroptosis independent of IRP1 and FBXL5 [J ] . Sci Adv , 2021 , 7 ( 22 ): eabg4302 .
HE X , ZHANG J Q , GONG M L , et al . Identification of potential ferroptosis⁃associated biomarkers in rheumatoid arthritis [J ] . Front Immunol , 2023 , 14 : 1197275 .
YAO X M , LI W , FANG D , et al . Emerging roles of energy metabolism in ferroptosis regulation of tumor cells [J ] . Adv Sci (Weinh) , 2021 , 8 ( 22 ): e2100997 .
XIANG J , CHEN H , LIN Z , et al . Identification and experimental validation of ferroptosis⁃related gene SLC2A3 is involved in rheumatoid arthritis [J ] . Eur J Pharmacol , 2023 , 943 : 175568 .
0
浏览量
11
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