Profiling gene expression induced by protease-activated receptor 2 (PAR2) activation in human kidney cells

Suen, JY, Gardiner, B, Grimmond, S and Fairlie, DP (2010) Profiling gene expression induced by protease-activated receptor 2 (PAR2) activation in human kidney cells. PLoS One, 5 11: e13809-1-e13809-14. doi:10.1371/journal.pone.0013809

Author Suen, JY
Gardiner, B
Grimmond, S
Fairlie, DP
Title Profiling gene expression induced by protease-activated receptor 2 (PAR2) activation in human kidney cells
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2010-11
Sub-type Article (original research)
DOI 10.1371/journal.pone.0013809
Open Access Status DOI
Volume 5
Issue 11
Start page e13809-1
End page e13809-14
Total pages 14
Place of publication San Francisco, United States
Publisher Public Library of Science
Collection year 2011
Language eng
Formatted abstract
Protease-Activated Receptor-2 (PAR2) has been implicated through genetic knockout mice with cytokine regulation and
arthritis development. Many studies have associated PAR2 with inflammatory conditions (arthritis, airways inflammation,
IBD) and key events in tumor progression (angiogenesis, metastasis), but they have relied heavily on the use of single
agonists to identify physiological roles for PAR2. However such probes are now known not to be highly selective for PAR2,
and thus precisely what PAR2 does and what mechanisms of downstream regulation are truly affected remain obscure.
Effects of PAR2 activation on gene expression in Human Embryonic Kidney cells (HEK293), a commonly studied cell line in
PAR2 research, were investigated here by comparing 19,000 human genes for intersecting up- or down-regulation by both
trypsin (an endogenous protease that activates PAR2) and a PAR2 activating hexapeptide (2f-LIGRLO-NH2). Among 2,500
human genes regulated similarly by both agonists, there were clear associations between PAR2 activation and cellular
metabolism (1,000 genes), the cell cycle, the MAPK pathway, HDAC and sirtuin enzymes, inflammatory cytokines, and anticomplement
function. PAR-2 activation up-regulated four genes more than 5 fold (DUSP6, WWOX, AREG, SERPINB2) and
down-regulated another six genes more than 3 fold (TXNIP, RARG, ITGB4, CTSD, MSC and TM4SF15). Both PAR2 and PAR1
activation resulted in up-regulated expression of several genes (CD44, FOSL1, TNFRSF12A, RAB3A, COPEB, CORO1C, THBS1,
SDC4) known to be important in cancer. This is the first widespread profiling of specific activation of PAR2 and provides a
valuable platform for better understanding key mechanistic roles of PAR2 in human physiology. Results clearly support the
development of both antagonists and agonists of human PAR2 as potential disease modifying therapeutic agents. © 2010 Suen et al.
Keyword Histone deacetylase inhibitors
Proinflammatory role
Coupled receptors
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article# e13809, pp.1-14

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 26 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 21 Nov 2010, 00:01:08 EST