PAR-2 activation increases human intestinal mucin secretion through EGFR transactivation
PAR-2 activation increases human intestinal mucin secretion through EGFR transactivation
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DOI：
10.1016/j.bbrc.2007.10.073
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发表时间：
2007-12-21
影响因子：
3.1
通讯作者：
Darmoul, Dalila
中科院分区：
文献类型：
--
作者：
Jarry, Anne;Dorso, Laetitia;Darmoul, Dalila
PAR - 2（蛋白酶激活受体 - 2）是G蛋白偶联受体，其对肠上皮细胞黏蛋白分泌的作用尚不清楚。本研究的目的是检测PAR - 2激活对人结肠杯状细胞系HT29 - Cl.16E中黏蛋白分泌的影响以及所涉及的细胞内通路。我们发现HT29 - Cl.16E细胞以及分离的人正常结肠细胞均组成性表达PAR - 2 mRNA。PAR - 2激活肽SLIGKV - NH₂可引起HT29 - Cl.16E中黏蛋白快速分泌，该分泌可被钙螯合剂BAPTA部分抑制。MAPK激活抑制剂（PD98059）和表皮生长因子受体（EGFR）酪氨酸激酶活性抑制剂（AG1478）分别消除了PAR - 2诱导的ERK1/2和EGFR酪氨酸磷酸化以及随后的黏蛋白分泌。最后，PAR - 2诱导的EGFR反式激活参与了ERK1/2激活的上游过程。我们的研究结果表明，人肠上皮细胞表达的PAR - 2的激活可通过涉及EGFR反式激活的通路增强黏蛋白分泌，黏蛋白分泌是肠道固有防御的一个组成部分。（C）2007爱思唯尔公司。保留所有权利。
PAR-2 (protease-activated receptors-2) are G protein-coupled receptors whose action on mucin secretion by intestinal epithelial cells is still unknown. The aim of this study was to examine the effect of PAR-2 activation on mucin secretion in the human colonic goblet cell line HT29-Cl.16E and the intracellular pathways involved. We found that PAR-2 mRNA was constitutively expressed by HT29-Cl.16E cells as well as by isolated human normal colonocytes. The PAR-2-activating peptide SLIGKV-NH2 elicited rapid mucin secretion in HT29-Cl.16E, which was partially inhibited by calcium chelator BAPTA. Inhibitors of MAPK activation (PD98059) and EGFR tyrosine kinase activity (AG1478) abrogated PAR-2-induced ERK1/2 and EGFR tyrosine phosphorylation, respectively, and subsequent mucin secretion. Finally, PAR-2-induced EGFR transactivation was involved upstream of ERK1/2 activation. Our results show that the activation of PAR-2 expressed by human intestinal epithelial cells enhances mucin secretion, a component of the intestinal innate defence, via a pathway involving EGFR transactivation. (C) 2007 Elsevier Inc. All rights reserved.