Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 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\25055964
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Toxicol+Sci
2014 ; 141
(2
): 515-23
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Toxicogenomic analysis reveals profibrogenic effects of trichloroethylene in
autoimmune-mediated cholangitis in mice
#MMPMID25055964
Kopec AK
; Sullivan BP
; Kassel KM
; Joshi N
; Luyendyk JP
Toxicol Sci
2014[Oct]; 141
(2
): 515-23
PMID25055964
show ga
Epidemiological studies suggest that exposure to environmental chemicals
increases the risk of developing autoimmune liver disease. However, the identity
of specific chemical perpetrators and the mechanisms whereby environmental
chemicals modify liver disease is unclear. Previous studies link exposure to
trichloroethylene (TCE) with the development of autoimmune liver disease and
exacerbation of autoimmunity in lupus-prone MRL mice. In this study, we utilized
NOD.c3c4 mice, which spontaneously develop autoimmune cholangitis bearing
resemblance to some features of primary biliary cirrhosis. Nine-week-old female
NOD.c3c4 mice were given TCE (0.5 mg/ml) or its vehicle (1% Cremophor-EL) in
drinking water for 4 weeks. TCE had little effect on clinical chemistry, biliary
cyst formation, or hepatic CD3+ T-cell accumulation. Hepatic microarray profiling
revealed a dramatic suppression of early growth response 1 (EGR1) mRNA in livers
of TCE-treated mice, which was verified by qPCR and immunohistochemical staining.
Consistent with a reported link between reduced EGR1 expression and liver
fibrosis, TCE increased hepatic type I collagen (COL1A1) mRNA and protein levels
in livers of NOD.c3c4 mice. In contrast, TCE did not increase COL1A1 expression
in NOD.ShiLtJ mice, which do not develop autoimmune cholangitis. These results
suggest that in the context of concurrent autoimmune liver disease with a genetic
basis, modification of hepatic gene expression by TCE may increase profibrogenic
signaling in the liver. Moreover, these studies suggest that NOD.c3c4 mice may be
a novel model to study gene-environment interactions critical for the development
of autoimmune liver disease.