scholarly journals Glucocorticoid receptor overexpression in forebrain: A mouse model of increased emotional lability

2004 ◽  
Vol 101 (32) ◽  
pp. 11851-11856 ◽  
Author(s):  
Q. Wei ◽  
X.-Y. Lu ◽  
L. Liu ◽  
G. Schafer ◽  
K.-R. Shieh ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1515
Author(s):  
Keiichiro Okuda ◽  
Atsushi Umemura ◽  
Shiori Umemura ◽  
Seita Kataoka ◽  
Hiroyoshi Taketani ◽  
...  

Non-alcoholic steatohepatitis (NASH) has become a serious public health problem associated with metabolic syndrome. The mechanisms by which NASH induces hepatocellular carcinoma (HCC) remain unknown. There are no approved drugs for treating NASH or preventing NASH-induced HCC. We used a genetic mouse model in which HCC was induced via high-fat diet feeding. This mouse model strongly resembles human NASH-induced HCC. The natural product honokiol (HNK) was tested for its preventative effects against NASH progression to HCC. Then, to clarify the mechanisms underlying HCC development, human HCC cells were treated with HNK. Human clinical specimens were also analyzed to explore this study’s clinical relevance. We found that epidermal growth factor receptor (EGFR) signaling was hyperactivated in the livers of mice with NASH and human HCC specimens. Inhibition of EGFR signaling by HNK drastically attenuated HCC development in the mouse model. Mechanistically, HNK accelerated the nuclear translocation of glucocorticoid receptor (GR) and promoted mitogen-inducible gene 6 (MIG6)/ERBB receptor feedback inhibitor 1 (ERRFI1) expression, leading to EGFR degradation and thereby resulting in robust tumor suppression. In human samples, EGFR-positive HCC tissues and their corresponding non-tumor tissues exhibited decreased ERRFI1 mRNA expression. Additionally, GR-positive non-tumor liver tissues displayed lower EGFR expression. Livers from patients with advanced NASH exhibited decreased ERRFI1 expression. EGFR degradation or inactivation represents a novel approach for NASH–HCC treatment and prevention, and the GR–MIG6 axis is a newly defined target that can be activated by HNK and related compounds.


2009 ◽  
Vol 379 (2) ◽  
pp. 406-410 ◽  
Author(s):  
Luis Escribano ◽  
Ana-María Simón ◽  
Alberto Pérez-Mediavilla ◽  
Pablo Salazar-Colocho ◽  
Joaquín Del Río ◽  
...  

2019 ◽  
Vol 29 ◽  
pp. S652
Author(s):  
F. Abdallah ◽  
S. Poggini ◽  
N. Ciano Albanese ◽  
V. Malpassuti ◽  
G. Matte Bon ◽  
...  

PLoS ONE ◽  
2009 ◽  
Vol 4 (12) ◽  
pp. e8202 ◽  
Author(s):  
Simone Wüst ◽  
Denise Tischner ◽  
Michael John ◽  
Jan P. Tuckermann ◽  
Christiane Menzfeld ◽  
...  

2017 ◽  
Vol 29 (5) ◽  
pp. 1795-1806 ◽  
Author(s):  
Dante Cicchetti ◽  
Elizabeth D. Handley

AbstractThe present study examined the effect of various dimensions of child maltreatment (i.e., developmental timing of maltreatment, number of maltreatment subtypes, and chronicity of maltreatment) on methylation of the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), and investigated the associations betweenNR3C1methylation and child outcomes. Participants included 534 children who attended a research summer camp program for school-aged maltreated (53.4%) and nonmaltreated (46.6%) children from low socioeconomic backgrounds. Results show that children with early onset maltreatment evidence significant hypermethylation compared to nonmaltreated children. Moreover, more maltreatment subtypes experienced and more chronic maltreatment are both related to greaterNR3C1hypermethylation. Findings also indicate that hypermethylation ofNR3C1is linked with a number of negative child outcomes including greater emotional lability–negativity, higher levels of ego undercontrol, more externalizing behavior, and greater depressive symptoms. Together, results highlight the role of methylation ofNR3C1in the effects of child maltreatment on the development of emotion dysregulation and psychopathology.


2005 ◽  
Vol 524 (1-3) ◽  
pp. 80-83 ◽  
Author(s):  
Ichiro Takasaki ◽  
Takashi Kurihara ◽  
Hironao Saegusa ◽  
Shuqin Zong ◽  
Tsutomu Tanabe

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