PAR-2 activation increases human intestinal mucin secretion through EGFR transactivation.
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-NH(2) 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.
Jarry
Anne
A
INSERM, U539, Nantes, F-44035, France.
Dorso
Laetitia
L
Gratio
Valérie
V
Forgue-Lafitte
Marie-Elisabeth
ME
Laburthe
Marc
M
Laboisse
Christian L
CL
Darmoul
Dalila
D
D020013:Calcium Signaling; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000235:genetics*; D005786:Gene Expression Regulation; D019073:HT29 Cells; D006801:Humans; D007419:Intestinal Secretions / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009077:Mucins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics*
D009077:Mucins; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases