紧密连接对肺通透性影响的研究进展

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (2): 272-276.

紧密连接对肺通透性影响的研究进展

武勰, 晏馥霞^*

中国医学科学院北京协和医学院国家心血管病中心阜外医院麻醉中心, 北京 100037

收稿日期:2020-01-14 修回日期:2020-05-25 出版日期:2021-02-05 发布日期:2021-01-19
通讯作者: ^*yanfuxia@sina.com
基金资助:
国家自然科学基金(81870070)

Research progress on the effects of tight junction on lung permeability

WU Xie, YAN Fu-xia^*

Department of Anesthesiology, Fuwai Hospital, National Center for Cardiovascular Diseases, CAMS & PUMC, Beijing 100037, China

Received:2020-01-14 Revised:2020-05-25 Online:2021-02-05 Published:2021-01-19
Contact: ^*yanfuxia@sina.com

摘要/Abstract

摘要： 肺组织受损时,肺泡上皮屏障和肺微血管内皮屏障会随之遭到破坏,从而影响肺的通透性,造成严重的肺水肿。紧密连接是一种上皮与内皮细胞间均存在的蛋白复合物,具有栅栏和屏障功能,对肺通透性的调节至关重要。本文主要就紧密连接(TJs)对肺通透性影响的研究进展进行了综述,以便加深对这一问题的理解,从而为临床治疗提供新的思路。

关键词: 紧密连接, 肺通透性, 肺泡上皮屏障, 肺血管内皮屏障

Abstract: The alveolar epithelial barrier and the pulmonary microvascular endothelial barrier will be destroyed when the lung tissue is damaged, thus affecting the permeability of the lung and causing serious pulmonary edema. Tight junctions (TJs) are protein complex with “fences and barriers” function that exists in epithelial cells and endothelial cells, and are crucial to the regulation of lung permeability. This paper mainly reviews the research progress on the effects of tight junction proteins on lung permeability, which can deepen the understanding of this problem and provides new ideas for clinical treatment.

Key words: tight junctions, pulmonary permeability, alveolar epithelial barrier, pulmonary endothelial barrier

中图分类号:

R363

武勰, 晏馥霞. 紧密连接对肺通透性影响的研究进展[J]. 基础医学与临床, 2021, 41(2): 272-276.

WU Xie, YAN Fu-xia. Research progress on the effects of tight junction on lung permeability[J]. Basic & Clinical Medicine, 2021, 41(2): 272-276.

参考文献

[1] Parthasarathi K. The pulmonary vascular barrier: insights into structure, function, and regulatory mechanisms[J]. Adv Anat Embryol Cell Biol,2018,228:41-61.
[2] Weibel ER. On the tricks alveolar epithelial cells play to make a good lung[J]. Am J Respir Crit Care Med,2015,191:504-513.
[3] Herrero R, Sanchez G, Lorente JA. New insights into the mechanisms of pulmonary edema in acute lung injury[J]. Ann Transl Med,2018,6:32.
[4] Heinemann U, Schuetz A. Structural features of tight-junction proteins[J]. Int J Mol Sci, 2019, 20:6020. doi:10.3390/ijms20236020.
[5] Yang J, Wang Y, Liu H, et al. C2-ceramide influences alveolar epithelial barrier function by downregulating Zo-1, occludin and claudin-4 expression[J]. Toxicol Mech Methods,2017,27:293-297.
[6] Otani T, Nguyen TP, Tokuda S, et al. Claudins and JAM-A coordinately regulate tight junction formation and epithelial polarity[J]. J Cell Biol,2019,218:3372-3396.
[7] Schlingmann B, Molina SA, Koval M. Claudins: gatekeepers of lung epithelial function[J]. Semin Cell Dev Biol,2015,42:47-57.
[8] Wittekindt OH. Tight junctions in pulmonary epithelia during lung inflammation[J]. Pflugers Arch,2017,469:135-147.
[9] Gan H, Wang G, Hao Q, et al. Protein kinase D promotes airway epithelial barrier dysfunction and permeability through down-regulation of claudin-1[J]. J Biol Chem,2013,288:37343-37354.
[10] Milatz S, Krug SM, Rosenthal R, et al. Claudin-3 acts as a sealing component of the tight junction for ions of either charge and uncharged solutes[J]. Biochim Biophys Acta,2010,1798:2048-2057.
[11] Kage H, Flodby P, Gao D, et al. Claudin 4 knockout mice: normal physiological phenotype with increased susceptibility to lung injury[J]. Am J Physiol Lung Cell Mol Physiol,2014,307:L524-L536.
[12] Kim DH, Lu Q, Chen YH. Claudin-7 modulates cell-matrix adhesion that controls cell migration, invasion and attachment of human HCC827 lung cancer cells[J]. Oncol Lett,2019,17:2890-2896.
[13] Kage H, Flodby P, Zhou B, et al. Dichotomous roles of claudins as tumor promoters or suppressors: lessons from knockout mice[J]. Cell Mol Life Sci,2019,76:4663-4672.
[14] Kotton DN. Claudin-18: unexpected regulator of lung alveolar epithelial cell proliferation[J]. J Clin Invest,2018,128:903-905.
[15] Van Itallie CM, Tietgens AJ, Anderson JM. Visualizing the dynamic coupling of claudin strands to the actin cytoskeleton through ZO-1[J]. Mol Biol Cell,2017,28:524-534.
[16] Rouaud F, Vasileva E, Spadaro D, et al. R40.76 binds to the alpha domain of ZO-1: role of ZO-1 (alpha+) in epithelial differentiation and mechano-sensing[J]. Tissue Barriers,2019,7:e1653748. doi: 10.1080/21688370.2019.1653748.
[17] Fu C, Hao S, Xu X, et al. Activation of SIRT1 ameliorates LPS-induced lung injury in mice via decreasing endothelial tight junction permeability[J]. Acta Pharmacol Sin,2019,40:630-641.
[18] Englert JA, Macias AA, Amador-Munoz D, et al. Isoflurane ameliorates acute lung injury by preserving epithelial tight junction integrity[J]. Anesthesiology,2015,123:377-388.
[19] Fang M, Zhong WH, Song WL, et al. Ulinastatin amelio-rates pulmonary capillary endothelial permeability induced by sepsis through protection of tight junctions via inhibition of TNF-alpha and related pathways[J]. Front Pharmacol,2018,9:823. doi: 10.3389/fphar.2018.00823.