Zhu Liling,Xiao Ting,Qu Shuangquan.HMGB1:a critical mediator and novel therapeutic target in the "lung-brain axis" inflammatory connection of acute lung injury[J].Journal of Clinical Pediatric Surgery,2025,(03):288-291.[doi:10.3760/cma.j.cn101785-202411008-016]
HMGB1:急性肺损伤“肺-脑轴”炎症关联的关键介质与治疗新靶标
- Title:
- HMGB1:a critical mediator and novel therapeutic target in the "lung-brain axis" inflammatory connection of acute lung injury
- Keywords:
- HMGB1; Acute Lung Injury; Lung-Brain Axis; Brain Injury
- 摘要:
- 急性肺损伤及其重症形式急性呼吸窘迫综合征均是高病死率的肺部疾病,常伴脑损伤,严重影响治疗与预后。炎症机制在急性肺损伤“肺-脑轴”中起关键作用,细胞外高迁移率族蛋白B1(high mobility group box1 protein,HMGB1)作为重要的促炎因子,广泛参与肺、脑损伤的发病过程。抑制HMGB1释放有望阻断肺-脑炎症沟通,为攻克肺脑共损伤提供新思路与治疗靶点。
- Abstract:
- Acute lung injury (ALI) and its more severe form,acute respiratory distress syndrome (ARDS),are lung diseases with high mortality rates.They are often complicated by brain injury,significantly affecting treatment and prognosis.Inflammatory plays a pivotal role in the "lung-brain axis" of ALI.As a critical pro-inflammatory factor,extracellular high mobility group box 1 protein (HMGB1) is widely implicated in the pathogenesis of both pulmonary and cerebral injuries.Inhibiting HMGB1 release is expected to disrupt inflammatory crosstalk between the lung and brain,offering novel insights and potential therapeutic targets for mitigating combined lung and brain damage.
参考文献/References:
[1] Hans-Peter K.Posttraumatic stress disorder in survivors of acute respiratory distress syndrome (ARDS) and septic shock[J].Psychosom Konsiliarpsychiatr,2008,2(4):220-227.DOI:10.1007/s11800-008-0129-x.
[2] Yuan JY,Guo L,Ma JT,et al.HMGB1 as an extracellular pro-inflammatory cytokine:implications for drug-induced organic damage[J].Cell Biol Toxicol,2024,40(1):55.DOI:10.1007/s10565-024-09893-2.
[3] Huang L,Wang MH,Yang XN,et al.Acute lung injury in patients with severe acute pancreatitis[J].Turk J Gastroenterol,2013,24(6):502-507.DOI:10.4318/tjg.2013.0544.
[4] Santiago VR,Andréia F Rzezinski,Nardelli LM,et al.Recruitment maneuver in experimental acute lung injury:the role of alveolar collapse and edema[J].Crit Care Med,2010,38(11):2207-2214.DOI:10.1097/CCM.0b013e3181f3e076.
[5] Hayashi K,Motoishi M,Sawai S,et al.Postoperative delirium after lung resection for primary lung cancer:risk factors,risk scoring system,and prognosis[J].PLoS One,2019,14(11):e0223917.DOI:10.1371/journal.pone.0223917.
[6] Murakawa K,Kitamura Y,Watanabe S,et al.Clinical risk factors associated with postoperative delirium and evaluation of delirium management and assessment team in lung and esophageal cancer patients[J].J Pharm Health Care Sci,2015,1(1):4.DOI:10.1186/s40780-014-0002-3.
[7] 曹书慧,寇久社,马三兴,等.肺-脑轴新机制及其研究进展[J].国际麻醉学与复苏杂志,2024,45(2):185-189.DOI:10.3760/cma.j.cn321761-20230506-00978. Cao SH,Kou JS,Ma SX,et al.New mechanism and research progress on the lung-brain axis[J].Int J Anesthesiol Resusc,2024,45(2):185-189.DOI:10.3760/cma.j.cn321761-20230506-00978.
[8] Wang Y,Mou YK,Wang HR,et al.Brain response in asthma:the role of "lung-brain" axis mediated by neuroimmune crosstalk[J].Front Immunol,2023,14:1240248.DOI:10.3389/fimmu.2023.1240248.
[9] 李春霞,周浩,崔玉霞.NLRP3在支气管哮喘"肺-脑轴"免疫炎症中的作用研究进展[J].中华实用儿科临床杂志,2022,37(13):1037-1040.DOI:10.3760/cma.j.cn101070-20210121-00090. Li CX,Zhou H,Cui YX.Research progress on the role of NLRP3 in the immune inflammation of the"lung-brain axis"of bronchial asthma[J].Chin J Appl Clin Pediatr,2022,37(13):1037-1040.DOI:10.3760/cma.j.cn101070-20210121-00090.
[10] Su YJ,Xu JH,Zhu ZA,et al.Brainstem Dbh+neurons control allergen-induced airway hyperreactivity[J].Nature,2024,631(8021):601-609.DOI:10.1038/s41586-024-07608-5.
[11] Ziaka M,Exadaktylos A.Pathophysiology of acute lung injury in patients with acute brain injury:the triple-hit hypothesis[J].Crit Care,2024,28(1):71.DOI:10.1186/s13054-024-04855-w.
[12] Tang DL,Kang R,Zeh HJ,et al.The multifunctional protein HM-GB1:50 years of discovery[J].Nat Rev Immunol,2023,23(12):824-841.DOI:10.1038/s41577-023-00894-6.
[13] Cui XH,Yao AH,Jia LY.Starvation insult induces the translocation of high mobility group box 1 to cytosolic compartments in glioma[J].Oncol Rep,2023,50(6):216.DOI:10.3892/or.2023.8653.
[14] Kanczkowski W,Alexaki VI,Tran N,et al.Hypothalamo-pituitary and immune-dependent adrenal regulation during systemic inflammation[J].Proc Natl Acad Sci U S A,2013,110(36):14801-14806.DOI:10.1073/pnas.1313945110.
[15] Nakao S,Yamaguchi K,Iwamoto H,et al.Serum high-mobility group box 1 as a predictive marker for cytotoxic chemotherapy-induced lung injury in patients with lung cancer and interstitial lung disease[J].Respir Med,2020,172:106131.DOI:10.1016/j.rmed.2020.106131.
[16] Liu Q,Xie WL,Wang YT,et al.JAK2/STAT1-mediated HMGB1 translocation increases inflammation and cell death in a ventilator-induced lung injury model[J].Lab Invest,2019,99(12):1810-1821.DOI:10.1038/s41374-019-0308-8.
[17] Huang Y,Wang AL,Jin S,et al.Activation of the NLRP3 inflammasome by HMGB1 through inhibition of the Nrf2/HO-1 pathway promotes bleomycin-induced pulmonary fibrosis after acute lung injury in rats[J].Allergol Immunopathol (Madr),2023,51(3):56-67.DOI:10.15586/aei.v51i3.668.
[18] Mo JL,Hu J,Cheng XL.The role of high mobility group box 1 in neuroinflammatory related diseases[J].Biomed Pharmacother,2023,161:114541.DOI:10.1016/j.biopha.2023.114541.
[19] Xu K,Wang MY,Wang HY,et al.HMGB1/STAT3/p65 axis drives microglial activation and autophagy exert a crucial role in chronic stress-induced major depressive disorder[J].J Adv Res,2024,59:79-96.DOI:10.1016/j.jare.2023.06.003.
[20] Bajinka O,Simbilyabo L,Tan YR,et al.Lung-brain axis[J].Crit Rev Microbiol,2022,48(3):257-269.DOI:10.1080/1040841X.2021.1960483.
[21] Chen RC,Zou J,Kang R,et al.The redox protein high-mobility group box 1 in cell death and cancer[J].Antioxid Redox Signal,2023,39(7/9):569-590.DOI:10.1089/ars.2023.0236.
[22] Gao B,Wang SW,Li JF,et al.HMGB1,angel or devil,in ischemic stroke[J].Brain Behav,2023,13(5):e2987.DOI:10.1002/brb3.2987.
[23] Aucott H,Lundberg J,Salo H,et al.Neuroinflammation in response to intracerebral injections of different HMGB1 redox isoforms[J].J Innate Immun,2018,10(3):215-227.DOI:10.1159/000487056.
[24] Moraes TR,Veras FP,Barchuk AR,et al.Spinal HMGB1 participates in the early stages of paclitaxel-induced neuropathic pain via microglial TLR4 and RAGE activation[J].Front Immunol,2024,15:1303937.DOI:10.3389/fimmu.2024.1303937.
[25] Paudel YN,Angelopoulou E,Piperi C,et al.Impact of HMGB1,RAGE,and TLR4 in Alzheimer’s disease (AD):from risk factors to therapeutic targeting[J].Cells,2020,9(2):383.DOI:10.3390/cells9020383.
[26] Lee JJ,Hsiao CC,Yang IH,et al.High-mobility group box 1 protein is implicated in advanced glycation end products-induced vascular endothelial growth factor A production in the rat retinal ganglion cell line RGC-5[J].Mol Vis,2012,18:838-850.
[27] Schilling T,Eder C.Importance of the non-selective cation channel TRPV1 for microglial reactive oxygen species generation[J].J Neuroimmunol,2009,216(1/2):118-121.DOI:10.1016/j.jneuroim.2009.07.008.
[28] Liu XW,Yuan L,Tang YS,et al.Da-Cheng-Qi decoction improves severe acute pancreatitis-associated acute lung injury by interfering with intestinal lymphatic pathway and reducing HMGB1-induced inflammatory response in rats[J].Pharm Biol,2023,61(1):144-154.DOI:10.1080/13880209.2022.2160768.
[29] Goldstein RS,Bruchfeld A,Yang LH,et al.Cholinergic anti-inflammatory pathway activity and High Mobility Group Box-1(HMGB1) serum levels in patients with rheumatoid arthritis[J].Mol Med,2007,13(3/4):210-215.DOI:10.2119/2006-00108.Goldstein.
[30] Wu D,Liao XM,Gao J,et al.A novel technique of cryodenervation for murine vagus nerve:implications for acute lung inflammation[J].Respir Res,2025,26(1):15.DOI:10.1186/s12931-025-03108-w.
[31] Tong J,Yao GH,Chen YQ,et al.Mesenchymal stem cells regulate microglial polarization via inhibition of the HMGB1/TLR4 signaling pathway in diabetic retinopathy[J].Inflammation,2024,47(5):1728-1743.DOI:10.1007/s10753-024-02005-6.
[32] Chen XD,Zhang JY,Kim B,et al.High-mobility group box-1 translocation and release after hypoxic ischemic brain injury in neonatal rats[J].Exp Neurol,2019,311:1-14.DOI:10.1016/j.expneurol.2018.09.007.
[33] Frasch MG,Szynkaruk M,Prout AP,et al.Decreased neuroinflammation correlates to higher vagus nerve activity fluctuations in near-term ovine fetuses:a case for the afferent cholinergic anti-inflammatory pathway?[J].J Neuroinflammation,2016,13(1):103.DOI:10.1186/s12974-016-0567-x.
[34] Wang H,Liao H,Ochani M,et al.Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis[J].Nat Med,2004,10(11):1216-1221.DOI:10.1038/nm1124.
[35] Lu ZB,Xie P,Zhang DM,et al.3-Dehydroandrographolide protects against lipopolysaccharide-induced inflammation through the cholinergic anti-inflammatory pathway[J].Biochem Pharmacol,2018,158:305-317.DOI:10.1016/j.bcp.2018.10.034.
[36] Chen WJ,Chen YP,Cheng WJ,et al.Acupuncture exerts preventive effects in rats of chronic unpredictable mild stress:the involvement of inflammation in amygdala and brain-spleen axis[J].Biochem Biophys Res Commun,2023,646:86-95.DOI:10.1016/j.bbrc.2023.01.046.
[37] Banks WA,Hansen KM,Erickson MA,et al.High-mobility group box 1(HMGB1) crosses the BBB bidirectionally[J].Brain Behav Immun,2023,111:386-394.DOI:10.1016/j.bbi.2023.04.018.
备注/Memo
收稿日期:2024-11-3。
基金项目:湖南省自然科学基金面上项目(2024JJ5220)
通讯作者:屈双权,Email:shuangquanqu@126.com