CHINESE JOURNAL OF MEDICINAL GUIDE >
Mechanism of TAX1BP1 and A20 Ubiquitination in Regulating NF-κB Pathway in Heart Failure
Received date: 2025-07-14
Revised date: 2026-01-23
Accepted date: 2026-03-18
Online published: 2026-04-21
Objective： To investigate the effect of Tax1 binding protein 1 （TAX1BP1） in synergy with zinc finger protein A20 on regulating the NF-κB pathway via ubiquitination in rats with heart failure.Methods： Ninety healthy rats were divided into five groups： control， TAX1BP1/A20 double-silenced （TADS）， TAX1BP1-silenced （TAS）， TAX1BP1-expressed （TAE）， and TAX1BP1/A20 double-expressed （TADE）. An isoproterenol-induced HF model was established. Myocardial ultrastructure was observed by transmission electron microscopy. Cardiomyocyte apoptosis was detected by TUNEL assay， and myocardial fibrosis was assessed by Masson’s trichrome staining. Levels of B-type natriuretic peptide （BNP）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in myocardial tissue were measured by ELISA. Hemodynamic parameters were recorded using the MedLab bio-signal processing system. Protein expression levels of microtubule-associated protein 1 light chain 3 II （LC3II）， LC3I， Beclin1， NF-κB inhibitory protein （IκB）， and phosphorylated IκB （p-IκB） were analyzed by Western blotting.Results： Compared with the control group， the TADS group showed more severe myocardial tissue injury. The cardiomyocyte apoptosis rate， myocardial fibrosis area ratio， serum levels of BNP， TNF-α， and IL-6， left ventricular end-diastolic pressure （LVEDP）， and the p-IκB/IκB protein expression ratio were significantly increased （P<0.05）， while the maximum rates of left ventricular pressure rise and fall （+dp/dtmax and -dp/dtmax） and the expression levels of LC3II/LC3I and Beclin1 were significantly decreased （P<0.01）. Compared with the TADS group， myocardial tissue injury was alleviated in the other intervention groups （TAS， TAE， TADE）. The cardiomyocyte apoptosis rate， myocardial fibrosis area， serum levels of BNP， IL-6， and TNF-α， LVEDP， and p-IκB/IκB expression were significantly decreased （P<0.05）， whereas+dp/dtmax， -dp/dtmax， and the expression levels of LC3II/LC3I and Beclin1 were sign ificantly increased （P<0.01）.Conclusion： TAX1BP1， in synergy with A20， alleviates myocardial cell injury in heart failure rats by suppressing the activation of the NF-κB signaling pathway. The signaling axis formed by these molecules provides an experimental basis and therapeutic strategy for targeted intervention in heart failure.
Key words： ; TAX1BP1； ; A20； ; NF-κB signaling pathway； ; Heart failure； ; Ubiquitination； ; Rat model
ZHANG Songquan, MA Hailong, SHAO Ke, LIANG Yan
.
Mechanism of TAX1BP1 and A20 Ubiquitination in
Regulating NF-κB Pathway in Heart Failure
［1］ World Health Organization.World health statistics 2024：monitoring health for the SDGs ［R］.Geneva： World Health Organization，2024：120.
［2］ 王朋飞，裴源源，石芳娥，等.急诊急性心力衰竭单元收治患者出院后6个月内再入院率和病死率分析［J］.中华急诊医学杂志， 2022，31（7）：886-894.
［3］ 王华，刘宇佳，杨杰孚.心力衰竭流行病学［J］.临床心血管病杂志，2023，39（4）：243-247.
［4］ 钮岳岳，侯承志，程晓振，等.射血分数改善/恢复的心力衰竭患者全因死亡率、再住院率及复合终点发生率的Meta分析［J］.实用心脑肺血管病杂志，2023，31（9）：74-80.
［5］ Jeffrey C， Nalin A， Teresa R， et al. Tax1bp1 enhances bacterial virulence and promotes inflammatory responses during mycobacterium tuberculosis infection of alveolar macrophages［J］. Bio Rxiv， 2024，10：1101.
［6］ Triposkiadis F， Xanthopoulos A， Parissis J， et al. Pathogenesis of chronic heart failure： cardiovascular aging， risk factors， comorbidities， and disease modifiers［J］.Heart Fail Rev， 2022，27（1）：337-344.
［7］ Shi Hui，Zhou Peng，Gao Ge，et al. Astragaloside IV prevents acute myocardial infarction by inhibiting the TLR4/MyD88/NF-kB signaling pathway［J］.J Food Biochem，2021， 45（7）：e13757-e14802.
［8］ 李超，陈云，李梅，等.南葶苈子对慢性心力衰竭大鼠心功能及SIRT2/NF-κB通路的影响［J］.中成药，2025，47（5）：1741-1745.
［9］ Zhang Rui， Xu Lin， Zhang Dong， et al. Cardioprotection of ginkgolide B on myocardial ischemia/reperfusion induced inflammatory injury via regulation of A20-NFkB pathway［J］.Front Immunol，2018，9（10）：2844-2858.
［10］ Tian Qian， Huo Bengang， Deng Xiaorong， et al. Decreased TAX1BP1 participates in systemic lupus erythematosus by regulating monocyte/macrophage function［J］. Int Immunol，2023，35（10）：483-495.
［11］ Wu Xintong，Zhang Zhonghong，Zhang Xiao， et al.Upregulation of A20 and TAX1BP1 contributes to the anti-neuroinflammatory and antidepressant effects of bavachalcone［J］.Int Immunopharmacol，2023，122（95）：110552-110998.
［12］ Li Bei，Zhang Yong，Liu Xinyuan，et al.Traditional Chinese medicine pien-tze-huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling［J］.J Pharm Anal， 2024，14（4）：601-614.
［13］ 马宏梅.电针上调Tax1结合蛋白1表达抑制大鼠局灶脑缺血/再灌注炎性损伤［D］.重庆：重庆医科大学，2018.
［14］ Villalvazo P，Carriazo S，Rojas-Rivera J，et al. Gain-of-function TLR7 and loss-of-function A20 gene variants identify a novel pathway for mendelian cupus and cupus nephritis［J］.Clin Kidney J， 2022，15（11）：1973-1980.
［15］ Savarese G， Becher PM， Lund LH， et al. Global burden of heart failure： comprehensive and updated review of epidemiology［J］.Cardiovasc Res，2023，118（17）：3272-3287.
［16］ Niu Jianli， Jin Zhuqing， Hyunbae K， et al. MCP-1-induced protein attenuates post-infarct cardiac remodeling and dysfunction through mitigating NF-κB activation and suppressing inflammation-associated microRNA expression［J］.Basic Res Cardiol， 2015，110（3）：26.
［17］ 庄梦梦，朱林平，李晓凤.基于NF-κB信号通路探讨中医药防治心力衰竭研究进展［J］.中医学报，2024，39（5）：994-1001.
［18］ Zuo Guangfeng，Wang Liguo， Huang Lu，et al.TAX1BP1 downregulation by STAT3 in cardiac fibroblasts contributes to diabetes-induced heart failure with preserved ejection fraction［J］. Biochim Biophys Acta Mol Basis Dis， 2024， 1870（2）：166979-167014.
［19］ 袁静蕾，廖志权，张瑞，等.选择性自噬受体TAX1BP1的研究进展及意义［J］.中国细胞生物学学报，2022，44（3）：492-499.
［20］ Dixit VM，Green S，Sarma V，et al.Tumor necrosis factor-alpha induction of novel gene products in human endothelial cells including a macrophage-specific chemotaxin［J］.J Biol Chem， 1990，265（5）：2973-2978.
［21］ Dario P， Geert YL， Mathieu JM， et al.A20 and cell death-driven inflammation［J］.Trends Immunology， 2020，41（5）：421-435.
［22］ Gabriela S， Bénédicte M， Arnaud M. TAX1BP1 a novel player in antigen presentation［J］.Autophagy， 2023，19（7）：2153-2155.
［23］ Zhang Ruoxi，Yu Chunhua，Herbert J，et al.TAX1BP1-dependent autophagic degradation of STING1 impairs anti-tumor immunity［J］.Autophagy，2025， 11（15）：1-22.
［24］ Bai Wenya，Huo Siying，Li Junjie，et al.Advances in the study of the ubiquitin-editing enzyme A20［J］. Front Pharmacol， 2022，10（13）：845262-845304.
［25］ Lawrence T. The nuclear factor NF-kappaB pathway inflammation［J］.Cold Spring Harb Perspect Biol， 2009，1（6）：1651-1694.
［26］ Qin Meng， Luo Yun， Lu Shan， et al.Ginsenoside FI ameliorates endothelial cell inflammatory injury and prevents atherosclerosis in mice through A20-mediated suppression of NF-kB signaling［J］.Front Pharmacol， 2017，8（9）：953-997.
［27］ Li Jiaqi， Yang Zhiping， Zhao Jie，et al. Nomilin alleviates neuroinflammation and depressive-like behaviors in mice through the upregulation of TAX1BP1-mediated modulation of microglia Polarization［J］.ACS Chem Neurosci， 2025，16（15）：3051-3058.
［28］ Yang Mei， Liu Xueting， Jiang Manli， et al. TAX1BP1/A20 inhibited TLR2-NF-κB activation to induce tolerant expression of IL-6 in endothelial cells.［J］.Int Immunopharmacol，2024， 30（139）：112789-112812.
［29］ Wu Zhifen，Tan Wei，Wang Chunxuan，et al.TAX1BP1 regulates the apoptosis of renal tubular epithelial cells in ischemia/reperfusion injury via the NF-kB/PMAIP1 signaling pathway［J］.Inflamm Res， 2025 Jan；74（1）：9-30.
［30］ 王海英，张宇琪，孙昊天，等.姜黄素及其衍生物的作用及机制［J］.生理科学进展，2022， 53（4）：271-275.
/
| 〈 |
|
〉 |