Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26439841
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 PLoS+Genet
2015 ; 11
(10
): e1005542
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
EP4 Receptor-Associated Protein in Macrophages Ameliorates Colitis and
Colitis-Associated Tumorigenesis
#MMPMID26439841
Nakatsuji M
; Minami M
; Seno H
; Yasui M
; Komekado H
; Higuchi S
; Fujikawa R
; Nakanishi Y
; Fukuda A
; Kawada K
; Sakai Y
; Kita T
; Libby P
; Ikeuchi H
; Yokode M
; Chiba T
PLoS Genet
2015[Oct]; 11
(10
): e1005542
PMID26439841
show ga
Prostaglandin E2 plays important roles in the maintenance of colonic homeostasis.
The recently identified prostaglandin E receptor (EP) 4-associated protein
(EPRAP) is essential for an anti-inflammatory function of EP4 signaling in
macrophages in vitro. To investigate the in vivo roles of EPRAP, we examined the
effects of EPRAP on colitis and colitis-associated tumorigenesis. In mice, EPRAP
deficiency exacerbated colitis induced by dextran sodium sulfate (DSS) treatment.
Wild-type (WT) or EPRAP-deficient recipients transplanted with EPRAP-deficient
bone marrow developed more severe DSS-induced colitis than WT or EPRAP-deficient
recipients of WT bone marrow. In the context of colitis-associated tumorigenesis,
both systemic EPRAP null mutation and EPRAP-deficiency in the bone marrow
enhanced intestinal polyp formation induced by azoxymethane (AOM)/DSS treatment.
Administration of an EP4-selective agonist, ONO-AE1-329, ameliorated DSS-induced
colitis in WT, but not in EPRAP-deficient mice. EPRAP deficiency increased the
levels of the phosphorylated forms of p105, MEK, and ERK, resulting in activation
of stromal macrophages in DSS-induced colitis. Macrophages of DSS-treated
EPRAP-deficient mice exhibited a marked increase in the expression of
pro-inflammatory genes, relative to WT mice. By contrast, forced expression of
EPRAP in macrophages ameliorated DSS-induced colitis and AOM/DSS-induced
intestinal polyp formation. These data suggest that EPRAP in macrophages
functions crucially in suppressing colonic inflammation. Consistently,
EPRAP-positive macrophages were also accumulated in the colonic stroma of
ulcerative colitis patients. Thus, EPRAP may be a potential therapeutic target
for inflammatory bowel disease and associated intestinal tumorigenesis.
free
free
free
