Regulation of MUC5AC mucin secretion by depletion of AQP5 in SPC-A1 cells
Regulation of MUC5AC mucin secretion by depletion of AQP5 in SPC-A1 cells
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DOI：
10.1016/j.bbrc.2006.01.103
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发表时间：
2006-04-14
影响因子：
3.1
通讯作者：
Bai, CX
中科院分区：
文献类型：
--
作者：
Chen, ZH;Wang, XD;Bai, CX
气道粘液受多种炎症介质如IL-1、TNF-α、EGF、PGF_（2 α）、LT等的调节，近年来，膜离子通道与粘液生成的关系受到研究。本研究旨在探讨AQP 5是否参与调节气道粘膜下腺细胞（SPC-Al）粘蛋白的表达和分泌。构建了含有靶向AQP 5序列的小发夹RNA表达盒的重组质粒pShAQP 5。pShAQP 5瞬时转染细胞后，ELISA检测显示MUC 5AC的合成和分泌在第5天分别增加了57.9%和85.3%。而在5个稳定转染的克隆（shAQP 5-G1、G2、G3、A2和A5）中，MMAC mRNA的表达水平分别上调了118%、165%、65%、123%和38%。MMAC合成和分泌的升高水平分别为59-156%和33- 166%。这是第一个可靠的调查MUC 5AC粘蛋白分泌的沉默AQP 5的调节。进一步研究AQP与粘蛋白之间的调节机制，可能为开发抗气道高分泌药物提供新的策略。(c)2006年爱思唯尔公司All rights reserved.
Airway mucus is regulated by many inflammatory mediators such as ILs, TNF-alpha, EGF, PGF2 alpha, LT, and so on. Recently, the relationship between membrane ion channel and Mucus production has been under investigation. The present study aimed to examine whether AQP5 was involved in modulation of mucin expression and secretion in airway submucosal gland cells (SPC-Al). A recombinant plasmid (pShAQP5) containing small hairpin RNA expression cassette targeting AQP5 sequence was constructed. In pShAQP5 transiently transfected cells, ELISA showed MUC5AC synthesis and secretion were increased by 57.9% and 85.3%, respectively, on day 5 after pShAQP5 transfection. While in five stably transfected clones (shAQP5-G1, G2, G3, A2, and A5), the upregulated levels of M MAC mRNA were 118%, 165%, 65% 123%, and 38%, respectively. The elevated levels of M MAC synthesis and secretion varied from 59-156% and 33-166%, respectively. This is the first reliable investigation of the regulation of MUC5AC mucin secretion by silencing AQP5. Further study of the regulatory mechanism between AQPs and mucins may provide new strategies for development of novel antihypersecretory drugs in airway diseases. (c) 2006 Elsevier Inc. All rights reserved.