Activation of transient receptor potential vanilloid subtype 1 increases secretion of the hypofunctional, transplanted submandibular gland.
Activation of transient receptor potential vanilloid subtype 1 increases secretion of the hypofunctional, transplanted submandibular gland.
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DOI：
10.1152/ajpgi.00528.2009
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发表时间：
2010-04
期刊：
影响因子：
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通讯作者：
Y. Zhang;X. Cong;L. Shi;L. Shi;Bin Xiang;Bin Xiang;Yu-ming Li;Yu-ming Li;Q. Ding
中科院分区：
文献类型：
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作者：
Y. Zhang;X. Cong;L. Shi;L. Shi;Bin Xiang;Bin Xiang;Yu-ming Li;Yu-ming Li;Q. Ding
多数严重干燥性角结膜炎患者自体颌下腺移植后早期出现分泌不足。内源性瞬时受体电位香草酸亚型1（TRPV1）最近已被证明在兔下颌下腺，并激活TRPV1辣椒素增加分泌在离体腺体，但TRPV1介导的分泌机制仍有待阐明。本研究旨在验证辣椒素激活TRPV1是否能改善移植腺的分泌功能及其机制。移植腺的唾液流量明显减少，TRPV1和水通道蛋白5（AQP5）的mRNA和蛋白水平下调。局部辣椒素乳膏增加了移植腺体的分泌，并上调了TRPV1和AQP5的水平。此外，在培养的下颌下腺细胞中，辣椒素增加了AQP5的mRNA表达，并导致AQP5从细胞质重新分布到质膜通过TRPV1激活。辣椒素增强细胞外信号调节激酶（ERK）的磷酸化。细胞与ERK激酶抑制剂PD98059预孵育，抑制辣椒素诱导的AQP5的mRNA表达。总之，辣椒素诱导的分泌机制涉及TRPV1的激活和ERK依赖的方式上调AQP5，并促进AQP5在颌下腺细胞中的重新分布。TRPV1的激活可能为改善下颌下腺功能减退提供一种新的治疗策略。
Hyposecretion occurs in most patients early after submandibular gland autotransplantation for severe keratoconjunctivitis sicca. Endogenous transient receptor potential vanilloid subtype 1 (TRPV1) has been recently demonstrated in rabbit submandibular glands, and activation of TRPV1 by capsaicin increases secretion in isolated glands, but the TRPV1-mediated secretory mechanism remains to be elucidated. The purpose of this study was to verify whether activation of TRPV1 by capsaicin could improve the secretion of transplanted gland and its underlying mechanism. The salivary flow of the transplanted glands was significantly decreased, and the mRNA and protein levels of TRPV1 and aquaporin 5 (AQP5) were downregulated in the transplanted glands. Topical capsaicin cream increased secretion and upregulated levels of TRPV1 and AQP5 in transplanted glands. Moreover, in cultured submandibular gland cells, capsaicin increased the mRNA expression of AQP5 and led to redistribution of AQP5 from the cytoplasm to the plasma membrane via TRPV1 activation. Capsaicin enhanced the phosphorylation of extracellular signal-regulated kinase (ERK). Preincubation of cells with PD98059, an inhibitor of ERK kinase, suppressed the capsaicin-induced mRNA expression of AQP5. In summary, the capsaicin-induced secretory mechanism involved activation of TRPV1 and upregulation of AQP5 in an ERK-dependent manner and promoted the redistribution of AQP5 in submandibular gland cells. Activation of TRPV1 may provide a new therapeutic strategy to improve submandibular gland hypofunction.