切换至 "中华医学电子期刊资源库"

第五届中国出版政府奖音像电子网络出版物奖提名奖

中国科技核心期刊

中国科学引文数据库(CSCD)来源期刊

中华重症医学电子杂志 ›› 2024, Vol. 10 ›› Issue (01) : 60 -65. doi: 10.3877/cma.j.issn.2096-1537.2024.01.010

综述

缝隙连接蛋白43在肺部疾病中的研究进展
李浩南1, 张煜彭1, 付焱1, 冯继伟1, 刘凯2, 张文凯2,()   
  1. 1. 030000 太原,山西医科大学第二临床医学院
    2. 030000 太原,山西医科大学第二医院重症医学科
  • 收稿日期:2023-06-15 出版日期:2024-02-28
  • 通信作者: 张文凯
  • 基金资助:
    山西省科技厅自然科学研究面上项目(202203021221278)

Advances in the study of Connexin 43 in lung diseases

Haonan Li1, Yupeng Zhang1, Yan Fu1, Jiwei Feng1, Kai Liu2, Wenkai Zhang2,()   

  1. 1. College of Second Clinical Medical, Shanxi Medical University, Taiyuan 030000, China
    2. Department of Intensive Care Unit, Second Hospital of Shanxi Medical University, Taiyuan 030000, China
  • Received:2023-06-15 Published:2024-02-28
  • Corresponding author: Wenkai Zhang
引用本文:

李浩南, 张煜彭, 付焱, 冯继伟, 刘凯, 张文凯. 缝隙连接蛋白43在肺部疾病中的研究进展[J/OL]. 中华重症医学电子杂志, 2024, 10(01): 60-65.

Haonan Li, Yupeng Zhang, Yan Fu, Jiwei Feng, Kai Liu, Wenkai Zhang. Advances in the study of Connexin 43 in lung diseases[J/OL]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2024, 10(01): 60-65.

缝隙连接蛋白43(Cx43)作为第一个被发现的缝隙连接蛋白,对胞间连接和通讯起着至关重要的作用,它在肺中的表达对于调节气-血屏障、通透性等有着极大影响。Cx43已被证实对急性肺损伤/急性呼吸窘迫综合征、哮喘、肺动脉高压、肺癌、新型冠状病毒感染等不同肺部疾病起到促进或抑制作用,其取决于介导的信号途径以及不同信号分子间的相互作用。本文旨在探讨Cx43在肺生长发育、损伤修复及多种肺部疾病中的作用,通过深入了解Cx43在这些疾病中的调控机制,有望为肺部疾病的预防、诊断和治疗提供新的视角,指导未来的研究和临床实践。

Connexin 43 (Cx43), as the first discovered connexin, plays a vital role in intercellular junction and communication, and its expression in the lung has a great influence on the regulation of the air-blood barrier and permeability. Cx43 was proven to promote or inhibit various lung diseases, including acute lung injury/acute respiratory distress syndrome, asthma, pulmonary hypertension, lung cancer, COVID-19, and others. It depends on the mediating signal pathway and the interaction of different signal molecules. We aim to investigate the function of Cx43 in lung growth and development, as well as its involvement in injury repair and various lung disorders. Through an comprehensive understanding of the regulatory mechanism of Cx43 in these diseases, it is expected that new insights will be provided for the prevention, diagnosis, and treatment of lung diseases, and guide future research and clinical practice.

1
Laird DW, Lampe PD. Therapeutic strategies targeting connexins [J]. Nat Rev Drug Discov, 2018, 17(12): 905-921.
2
Dbouk HA, Mroue RM, El-Sabban ME, et al. Connexins: a myriad of functions extending beyond assembly of gap junction channels [J]. Cell Commun Signal, 2009, 7: 4.
3
Rodjakovic D, Salm L, Beldi G. Function of Connexin-43 in macrophages [J]. Int J Mol Sci, 2021, 22(3): 1412.
4
Saez JC, Berthoud VM, Branes MC, et al. Plasma membrane channels formed by connexins: their regulation and functions [J]. Physiol Rev, 2003, 83(4): 1359-1400.
5
Kar R, Batra N, Riquelme MA, et al. Biological role of connexin intercellular channels and hemichannels [J]. Arch Biochem Biophys, 2012, 524(1): 2-15.
6
Zhang Q, Bai X, Liu Y, et al. Current concepts and perspectives on Connexin43: a mini review [J]. Curr Protein Pept Sci, 2018, 19(11): 1049-1057.
7
Martins-Marques T, Ribeiro-Rodrigues T, Batista-Almeida D, et al. Biological functions of Connexin43 beyond intercellular communication [J]. Trends Cell Biol, 2019, 29(10): 835-847.
8
Nagata K, Masumoto K, Esumi G, et al. Connexin43 plays an important role in lung development [J]. J Pediatr Surg, 2009, 44(12): 2296-2301.
9
Cai Q, Zhao X, Yu X, et al. The specific Connexin 43-inhibiting peptide gap26 improved alveolar development of neonatal rats with hyperoxia exposure [J]. Front Pharmacol, 2021, 12: 587267.
10
Johnson LN, Koval M. Cross-talk between pulmonary injury, oxidant stress, and gap junctional communication [J]. Antioxid Redox Signal, 2009, 11(2): 355-367.
11
Wright JR. The "wisdom" of lung surfactant: balancing host defense and surface tension-reducing functions [J]. Am J Physiol Lung Cell Mol Physiol, 2006, 291(5): L847-850.
12
Kasper M, Traub O, Reimann T, et al. Upregulation of gap junction protein connexin43 in alveolar epithelial cells of rats with radiation-induced pulmonary fibrosis [J]. Histochem Cell Biol, 1996, 106(4): 419-424.
13
O'Donnell JJ,3rd, Birukova AA, Beyer EC, et al. Gap junction protein connexin43 exacerbates lung vascular permeability [J]. PLoS One, 2014, 9(6): e100931.
14
Fanelli V, Ranieri VM. Mechanisms and clinical consequences of acute lung injury [J]. Ann Am Thorac Soc, 2015, 12(Suppl 1): S3-8.
15
Parthasarathi K. Endothelial connexin43 mediates acid-induced increases in pulmonary microvascular permeability [J]. Am J Physiol Lung Cell Mol Physiol, 2012, 303(1): L33-42.
16
Liu T, Li Y, Zhang B, et al. The role of phosphorylated Cx43 on PKC mediated Ser368 in lung injury induced by seawater inhalation [J]. Inflammation, 2015, 38(5): 1847-1854.
17
Zhou J, Fu Y, Liu K, et al. miR-206 regulates alveolar type Ⅱ epithelial cell Cx43 expression in sepsis-induced acute lung injury [J]. Exp Ther Med, 2019, 18(1): 296-304.
18
赵希伟, 周佳伟, 刘凯, 等. 连接蛋白43通过蛋白激酶A介导丝氨酸373调控脓毒症急性肺损伤肺泡Ⅱ型上皮细胞屏障功能的研究 [J/OL]. 中华危重症医学杂志(电子版), 2021, 14(5): 355-361.
19
Wang S, Sun Y, Bai Y, et al. Contribution of connexin hemichannels to the pathogenesis of acute lung injury [J]. Mediators Inflamm, 2020, 2020: 8094347.
20
Parthasarathi K, Ichimura H, Monma E, et al. Connexin 43 mediates spread of Ca2+-dependent proinflammatory responses in lung capillaries [J]. J Clin Invest, 2006, 116(8): 2193-2200.
21
Yao Y, Zeng QX, Deng XQ, et al. Connexin 43 upregulation in mouse lungs during ovalbumin-induced asthma [J]. PLoS One, 2015, 10(12): e0144106.
22
Paw M, Borek I, Wnuk D, et al. Connexin43 controls the myofibroblastic differentiation of bronchial fibroblasts from patients with asthma [J]. Am J Respir Cell Mol Biol, 2017, 57(1): 100-110.
23
Huang JQ, Chen XY, Huang F, et al. Effects of Connexin 43 Inhibition in an Ovalbumin-induced mouse model of asthma [J]. Iran J Allergy Asthma Immunol, 2018, 17(1): 29-38.
24
Billaud M, Dahan D, Marthan R, et al. Role of the gap junctions in the contractile response to agonists in pulmonary artery from two rat models of pulmonary hypertension [J]. Respir Res, 2011, 12(1): 30.
25
Chen M, Liu Y, Yi D, et al. Tanshinone ⅡA promotes pulmonary artery smooth muscle cell apoptosis in vitro by inhibiting the JAK2/STAT3 signaling pathway [J]. Cell Physiol Biochem, 2014, 33(4): 1130-1138.
26
Han XJ, Zhang WF, Wang Q, et al. HIF-1α promotes the proliferation and migration of pulmonary arterial smooth muscle cells via activation of Cx43 [J]. J Cell Mol Med, 2021, 25(22): 10663-10673.
27
Qin X, Hou X, Xu X, et al. Down-regulation of connexin 43 contributes to structure and function of pulmonary artery in nicotine-administered mice [J]. Toxicol Lett, 2023, 377: 1-13.
28
Zhang , Fan ZR, Wang L, et al. Carbenoxolone decreases monocrotaline‑induced pulmonary inflammation and pulmonary arteriolar remodeling in rats by decreasing the expression of connexins in T lymphocytes [J]. Int J Mol Med, 2020, 45(1): 81-92.
29
Boengler K, Rohrbach S, Weissmann N, et al. Importance of Cx43 for right ventricular function [J]. Int J Mol Sci, 2021, 22(3): 987.
30
Zang JP, Wei R. Effects of Cx43 gene modification on the proliferation and migration of the human lung squamous carcinoma cell line NCI-H226 [J]. Genet Mol Res, 2015, 14(4): 13110-13119.
31
Xu HT, Li QC, Zhang YX, et al. Connexin 43 recruits E-cadherin expression and inhibits the malignant behaviour of lung cancer cells [J]. Folia Histochem Cytobiol, 2008, 46(3): 315-321.
32
Zhao W, Han HB, Zhang ZQ. Suppression of lung cancer cell invasion and metastasis by Connexin43 involves the secretion of follistatin-like 1 mediated via histone acetylation [J]. Int J Biochem Cell Biol, 2011, 43(10): 1459-1468.
33
Ruch RJ. Connexin43 suppresses lung cancer stem cells [J]. Cancers (Basel), 2019, 11(2): 175.
34
Huang W, Wang Y, He T, et al. Arteannuin B enhances the effectiveness of Cisplatin in non-small cell lung cancer by regulating Connexin 43 and MAPK pathway [J]. Am J Chin Med, 2022, 50(7): 1963-1992.
35
Jones JC, Bodenstine TM. Connexins and glucose metabolism in cancer [J]. Int J Mol Sci, 2022, 23(17): 10172.
36
Luo M, Luo Y, Mao N, et al. Cancer-associated fibroblasts accelerate malignant progression of non-small cell lung cancer via Connexin 43-formed unidirectional gap junctional intercellular communication [J]. Cell Physiol Biochem, 2018, 51(1): 315-336.
37
Ni C, Lou X, Yao X, et al. ZIP1+ fibroblasts protect lung cancer against chemotherapy via connexin-43 mediated intercellular Zn2+ transfer [J]. Nat Commun, 2022, 13(1): 5919.
38
Cooreman A, Caufriez A, Tabernilla A, et al. Effects of drugs formerly proposed for COVID-19 treatment on Connexin43 hemichannels [J]. Int J Mol Sci, 2022, 23(9): 5018.
39
Eltzschig HK, Eckle T, Mager A, et al. ATP release from activated neutrophils occurs via connexin 43 and modulates adenosine-dependent endothelial cell function [J]. Circ Res, 2006, 99(10): 1100-1108.
40
Swartzendruber JA, Nicholson BJ, Murthy AK. The role of Connexin 43 in lung disease [J]. Life (Basel), 2020, 10(12): 363.
41
Peirouvi T, Aliaghaei A, Eslami Farsani B, et al. COVID-19 disrupts the blood-testis barrier through the induction of inflammatory cytokines and disruption of junctional proteins [J]. Inflamm Res, 2021, 70(10-12): 1165-1175.
42
Li MW, Mruk DD, Lee WM, et al. Connexin 43 is critical to maintain the homeostasis of the blood-testis barrier via its effects on tight junction reassembly [J]. Proc Natl Acad Sci U S A, 2010, 107(42): 17998-18003.
43
Machtaler S, Dang-Lawson M, Choi K, et al. The gap junction protein Cx43 regulates B-lymphocyte spreading and adhesion [J]. J Cell Sci, 2011, 124(Pt 15): 2611-2621.
44
Machtaler S, Choi K, Dang-Lawson M, et al. The role of the gap junction protein connexin43 in B lymphocyte motility and migration [J]. FEBS Lett, 2014, 588(8): 1249-1258.
45
Huang Y, Mao Z, Zhang Z, et al. Connexin43 contributes to inflammasome activation and lipopolysaccharide-initiated acute renal injury via modulation of intracellular oxidative status [J]. Antioxid Redox Signal, 2019, 31(16): 1194-1212.
46
Neijssen J, Pang B, Neefjes J. Gap junction-mediated intercellular communication in the immune system [J]. Prog Biophys Mol Biol, 2007, 94(1-2): 207-218.
47
Matsue H, Yao J, Matsue K, et al. Gap junction-mediated intercellular communication between dendritic cells (DCs) is required for effective activation of DCs [J]. J Immunol, 2006, 176(1): 181-190.
48
Feng YY, Tang M, Suzuki M, et al. Essential role of NADPH oxidase-dependent production of reactive oxygen species in maintenance of sustained B cell receptor signaling and B cell proliferation [J]. J Immunol, 2019, 202(9): 2546-2557.
49
Huang Y, Mao Z, Zhang X, et al. Connexin43 is required for the effective activation of spleen cells and immunoglobulin production [J]. Int J Mol Sci, 2019, 20(22): 5789.
50
Yao Y, Fan XL, Jiang D, et al. Connexin 43-mediated mitochondrial transfer of iPSC-MSCs alleviates asthma inflammation [J]. Stem Cell Reports, 2018, 11(5): 1120-1135.
51
Li X, Zhang Y, Yeung SC, et al. Mitochondrial transfer of induced pluripotent stem cell-derived mesenchymal stem cells to airway epithelial cells attenuates cigarette smoke-induced damage [J]. Am J Respir Cell Mol Biol, 2014, 51(3): 455-465.
52
Boengler K, Leybaert L, Ruiz-Meana M, et al. Connexin 43 in mitochondria: what do we really know about its function? [J]. Front Physiol, 2022, 13: 928934.
[1] 刘琴, 刘瀚旻, 谢亮. 基质金属蛋白酶在儿童哮喘发生机制中作用的研究现状[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(05): 564-568.
[2] 杨轲, 丁增巴姆, 马静, 李盼盼, 陈婷. 全程无缝隙肺康复训练在单孔胸腔镜肺叶切除术中的临床应用[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 801-804.
[3] 张礼江, 沈玲佳, 施我大. 倾向性评分匹配分析奥希替尼对晚期NSCLC 预后的影响[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 820-822.
[4] 钱春蕊, 周燕, 张晶, 蔡笃财, 门慧, 王松海, 黎莉, 邢龙. 高分辨率CT 与多层螺旋CT 在肺结节及早期肺癌中的应用[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 827-830.
[5] 袁延丽, 屈卓军, 崔会慧, 王菁, 高贝贝, 潘院. 原发性肺癌切除术后谵妄的危险因素及预后分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 701-706.
[6] 井发红, 李丽娜, 高婷, 高艳梅, 杨楠, 李卓, 慕玉东. 肺癌立体定向放疗血清SAP 和MMPs 表达及临床意义[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 707-713.
[7] 邢嘉翌, 龚佳晟, 祝佳佳, 陆群. 肺癌化疗患者继发肺部感染的病原菌耐药性及炎症因子变化分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 714-718.
[8] 杨慧, 郭丽娟, 冯晓丹, 李静, 黄成谋, 蔡兴锐, 覃英娇, 王远礼. 非小细胞肺癌铂类药物耐药mi RNA表达特征及预测分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 719-724.
[9] 张卫锋, 张天翼, 赵正维, 王海强, 尹逊亮. VE /VCO2 斜率对肺癌肺叶切除术后心血管并发症的预测意义[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 725-730.
[10] 赖淼, 景鑫, 李桂珍, 李怡. 非小细胞肺癌EGFR 突变亚型的临床病理和预后意义[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 731-737.
[11] 梁丽斯, 李洁, 贺帅, 来艳君, 刘铭, 张琳. MMP-9、MMP-2 及TLR4、HE4对非小细胞肺癌早期诊断意义[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 756-761.
[12] 赵蒙蒙, 黄洁, 余荣环, 王葆青. 过表达小GTP酶Rab32抑制非小细胞肺癌细胞侵袭性生长[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(04): 512-518.
[13] 张桂萍, 丘勇林, 湛绮婷, 孙乐栋. 晚期非小细胞肺癌血清Ape1/Ref-1对放射性肺损伤发生的预测意义[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(04): 519-523.
[14] 赵静, 范晔, 游雅婷, 陈慧, 王静, 张静. 虚拟支气管镜导航联合径向超声支气管镜在周围型肺癌中的诊断意义[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(04): 524-528.
[15] 刘一鸣, 温佳新, 赵恺, 薛志强. ⅢA 期肺腺癌新辅助治疗后胸腔镜右肺中下叶切除术[J/OL]. 中华腔镜外科杂志(电子版), 2024, 17(05): 311-313.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?