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学科主题: 口腔医学
题名:
Occludin is required for TRPV1-modulated paracellular permeability in the submandibular gland
作者: 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
发表日期: 2013-03-01
DOI: 10.1242/jcs.111781
卷: 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
所属项目编号: 81070847 ; 30730102 ; 81271161 ; 81170974
项目资助者: National Science Foundation of China
WOS记录号: WOS:000318015800008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50125
Appears in Collections:北京大学口腔医学院_期刊论文

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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

Recommended Citation:
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.
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