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Occludin is required for TRPV1-modulated paracellular permeability in the submandibular gland
Cong, Xin1,2; Zhang, Yan1,2; Yang, Ning-Yan3; Li, Jing3; Ding, Chong4; Ding, Qian-Wen5; Su, Yun-Chao1,2; Mei, Mei3; Guo, Xiao-Hong1,2; Wu, Li-Ling1,2; Yu, Guang-Yan3
关键词Occludin Submandibular Gland Tight Junction Transient Receptor Potential Vanilloid Subtype 1
刊名JOURNAL OF CELL SCIENCE
2013-03-01
DOI10.1242/jcs.111781
126期:5页:1109-1121
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cell Biology
研究领域[WOS]Cell Biology
关键词[WOS]TIGHT JUNCTION STRUCTURE ; LIGHT-CHAIN PHOSPHORYLATION ; BARRIER FUNCTION ; EPITHELIAL-CELLS ; IN-VIVO ; MEMBRANE-PROTEIN ; CHLORIDE CHANNEL ; SALIVARY-GLANDS ; F-ACTIN ; EXPRESSION
英文摘要

Occludin plays an important role in maintaining tight junction barrier function in many types of epithelia. We previously reported that activation of transient receptor potential vanilloid subtype 1 (TRPV1) in rabbit submandibular gland promoted salivary secretion, partly by an increase in paracellular permeability. We have now explored the role of occludin in TRPV1-modulated paracellular permeability in a rat submandibular gland cell line SMG-C6. Both TRPV1 and occludin were expressed in SMG-C6 cells, and capsaicin induced redistribution of occludin, but not claudin-3, claudin-4 or E-cadherin, from the cell membrane into the cytoplasm. Capsaicin also decreased transepithelial electrical resistance (TER) and increased the Trypan Blue and FITC-dextran flux. Capsazepine (CPZ), a TRPV1 antagonist, inhibited the capsaicin-induced occludin redistribution and TER decrease. Moreover, occludin knockdown by shRNA suppressed, whereas occludin re-expression restored, the TER response to capsaicin. Mechanistically, TRPV1 activation increased ERK1/2 and MLC2 phosphorylation. PD98059, an ERK1/2 kinase inhibitor, abolished the capsaicin-induced MLC2 phosphorylation, whereas ML-7, an MLC2 kinase inhibitor, did not affect ERK1/2 phosphorylation, suggesting that ERK1/2 is the upstream signaling molecule of MLC2. Capsaicin also induced F-actin reorganization, which was abolished by CPZ, PD98059 and ML-7, indicating that TRPV1 activation altered F-actin organization in an ERK1/2- and MLC2-dependent manner. Furthermore, either PD98059 or ML-7 could abolish the capsaicin-induced TER response and occludin redistribution, whereas knockdown of ERK1/2 further confirmed that the TRPV1-modulated paracellular permeability was ERK1/2 dependent. Taken together, these results identified a crucial role of occludin in submandibular epithelial cells, and more importantly, demonstrated that occludin was required to mediate TRPV1-modulated paracellular permeability.

语种英语
WOS记录号WOS:000318015800008
项目编号81070847 ; 30730102 ; 81271161 ; 81170974
资助机构National Science Foundation of China
引用统计
被引频次:23[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50125
专题北京大学口腔医学院
北京大学基础医学院
北京大学口腔医学院_外科
北京大学口腔医学院_中心实验室
作者单位1.Peking Univ, Peking Univ Sch & Hosp Stomatol, Dept Physiol & Pathophysiol, Ctr Salivary Gland Dis,Hlth Sci Ctr,Sch Basic Med, Beijing 100871, Peoples R China
2.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing, Peoples R China
3.Peking Univ Sch & Hosp Stomatol, Dept Oral & Maxillofacial Surg, Beijing, Peoples R China
4.Peking Univ Sch & Hosp Stomatol, Cent Lab, Beijing, Peoples R China
5.Capital Med Univ, Beijing Stomatol Hosp, Dept Dent Emergency, Beijing, Peoples R China
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GB/T 7714
Cong, Xin,Zhang, Yan,Yang, Ning-Yan,et al. Occludin is required for TRPV1-modulated paracellular permeability in the submandibular gland[J]. JOURNAL OF CELL SCIENCE,2013,126(5):1109-1121.
APA Cong, Xin.,Zhang, Yan.,Yang, Ning-Yan.,Li, Jing.,Ding, Chong.,...&Yu, Guang-Yan.(2013).Occludin is required for TRPV1-modulated paracellular permeability in the submandibular gland.JOURNAL OF CELL SCIENCE,126(5),1109-1121.
MLA Cong, Xin,et al."Occludin is required for TRPV1-modulated paracellular permeability in the submandibular gland".JOURNAL OF CELL SCIENCE 126.5(2013):1109-1121.
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