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氯离子通道蛋白2(ClC-2)对肠道屏障功能的调节:基础科学向治疗靶点的转化

ClC-2 regulation of intestinal barrier function: Translation of basic science to therapeutic target.

作者信息

Jin Younggeon, Blikslager Anthony T

机构信息

Department of Clinical Sciences; College of Veterinary Medicine, North Carolina State University ; Raleigh, NC, USA.

出版信息

Tissue Barriers. 2015 Nov 13;3(4):e1105906. doi: 10.1080/21688370.2015.1105906. eCollection 2015 Oct-Dec.

DOI:10.1080/21688370.2015.1105906
PMID:26716076
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4681285/
Abstract

The ClC-2 chloride channel is a member of the voltage-gated chloride channel family. ClC-2 is involved in various physiological processes, including fluid transport and secretion, regulation of cell volume and pH, maintaining the membrane potential of the cell, cell-to-cell communication, and tissue homeostasis. Recently, our laboratory has accumulated evidence indicating a critical role of ClC-2 in the regulation of intestinal barrier function by altering inter-epithelial tight junction composition. This review will detail the role of ClC-2 in intestinal barrier function during intestinal disorders, including experimental ischemia/reperfusion injury and dextran sodium sulfate (DSS)-induced inflammatory bowel disease. Details of pharmacological manipulation of ClC-2 via prostone agonists will also be provided in an effort to show the potential therapeutic relevance of ClC-2 regulation, particularly during intestinal barrier disruption.

摘要

氯离子通道蛋白2(ClC-2)是电压门控氯离子通道家族的成员之一。ClC-2参与多种生理过程,包括液体运输与分泌、细胞体积和pH值的调节、维持细胞的膜电位、细胞间通讯以及组织稳态。最近,我们实验室积累了证据,表明ClC-2通过改变上皮细胞间紧密连接的组成,在肠道屏障功能的调节中起关键作用。本综述将详细阐述ClC-2在肠道疾病(包括实验性缺血/再灌注损伤和葡聚糖硫酸钠(DSS)诱导的炎症性肠病)期间肠道屏障功能中的作用。还将提供通过前列腺素激动剂对ClC-2进行药理学调控的细节,以展示ClC-2调节的潜在治疗意义,尤其是在肠道屏障破坏期间。

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本文引用的文献

1
Pharmaceutical Activation or Genetic Absence of ClC-2 Alters Tight Junctions During Experimental Colitis.实验性结肠炎期间,ClC-2的药物激活或基因缺失会改变紧密连接。
Inflamm Bowel Dis. 2015 Dec;21(12):2747-57. doi: 10.1097/MIB.0000000000000550.
2
Differentiation between human ClC-2 and CFTR Cl- channels with pharmacological agents.用药物区分人 ClC-2 和 CFTR Cl- 通道。
Am J Physiol Cell Physiol. 2014 Sep 1;307(5):C479-92. doi: 10.1152/ajpcell.00077.2014. Epub 2014 Jul 9.
3
Chloride channel ClC-2 is a key factor in the development of DSS-induced murine colitis.氯离子通道 ClC-2 是 DSS 诱导的小鼠结肠炎发展的关键因素。
Inflamm Bowel Dis. 2013 Dec;19(13):2867-77. doi: 10.1097/MIB.0b013e3182a82ae9.
4
Occludin OCEL-domain interactions are required for maintenance and regulation of the tight junction barrier to macromolecular flux.封闭蛋白 OCEL 结构域相互作用对于维持和调节大分子通量的紧密连接屏障是必需的。
Mol Biol Cell. 2013 Oct;24(19):3056-68. doi: 10.1091/mbc.E12-09-0688. Epub 2013 Aug 7.
5
Lubiprostone Increases Small Intestinal Smooth Muscle Contractions Through a Prostaglandin E Receptor 1 (EP1)-mediated Pathway.鲁比前列酮通过前列腺素 E 受体 1(EP1)介导的途径增加小肠平滑肌收缩。
J Neurogastroenterol Motil. 2013 Jul;19(3):312-8. doi: 10.5056/jnm.2013.19.3.312. Epub 2013 Jul 8.
6
Cell biology and physiology of CLC chloride channels and transporters.CLC 氯离子通道和转运蛋白的细胞生物学和生理学。
Compr Physiol. 2012 Jul;2(3):1701-44. doi: 10.1002/cphy.c110038.
7
Lubiprostone decreases mouse colonic inner mucus layer thickness and alters intestinal microbiota.鲁比前列酮可减少小鼠结肠内黏液层厚度并改变肠道微生物群。
Dig Dis Sci. 2013 Mar;58(3):668-77. doi: 10.1007/s10620-012-2509-5. Epub 2013 Jan 18.
8
Dual activation of CFTR and CLCN2 by lubiprostone in murine nasal epithelia.利那洛肽激活小鼠鼻黏膜上皮细胞中的 CFTR 和 CLCN2。
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Gastro protective properties of the novel prostone SPI-8811 against acid-injured porcine mucosa.新型前列腺素 SPI-8811 对酸损伤猪黏膜的胃保护作用。
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