scholarly journals Dysfunction of estrogen-related receptor alpha-dependent hepatic VLDL secretion contributes to sex disparity in NAFLD/NASH development

Theranostics ◽  
2020 ◽  
Vol 10 (24) ◽  
pp. 10874-10891
Author(s):  
Meng Yang ◽  
Qingli Liu ◽  
Tongling Huang ◽  
Wenjuan Tan ◽  
Linbing Qu ◽  
...  
Keyword(s):  
Receptor Alpha ◽  
Vldl Secretion ◽  
Sex Disparity ◽  
Estrogen Related Receptor

scholarly journals Estrogen-related receptor alpha (ERRα) is a key regulator of intestinal homeostasis and protects against colitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Allan Tran ◽  
Charlotte Scholtes ◽  
Mario Songane ◽  
Claudia Champagne ◽  
Luc Galarneau ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Current Knowledge ◽  
Experimental Colitis ◽  
Protective Effects ◽  
Mitochondrial Energy Metabolism ◽  
Receptor Alpha ◽  
Cell Counts ◽  
Α Diversity ◽  
Estrogen Related Receptor

AbstractThe estrogen-related receptor alpha (ERRα) is a primary regulator of mitochondrial energy metabolism, function and dynamics, and has been implicated in autophagy and immune regulation. ERRα is abundantly expressed in the intestine and in cells of the immune system. However, its role in inflammatory bowel disease (IBD) remains unknown. Here, we report a protective role of ERRα in the intestine. We found that mice deficient in ERRα were susceptible to experimental colitis, exhibiting increased colon inflammation and tissue damage. This phenotype was mediated by impaired compensatory proliferation of intestinal epithelial cells (IEC) following injury, enhanced IEC apoptosis and necrosis and reduced mucus-producing goblet cell counts. Longitudinal analysis of the microbiota demonstrated that loss of ERRα lead to a reduction in microbiome α-diversity and depletion of healthy gut bacterial constituents. Mechanistically, ERRα mediated its protective effects by acting within the radio-resistant compartment of the intestine. It promoted disease tolerance through transcriptional control of key genes involved in intestinal tissue homeostasis and repair. These findings provide new insights on the role of ERRα in the gut and extends our current knowledge of nuclear receptors implicated in IBD.

scholarly journals Anti-tumor effect of estrogen-related receptor alpha knockdown on uterine endometrial cancer

Oncotarget ◽  
2016 ◽  
Vol 7 (23) ◽  
pp. 34131-34148 ◽  
Author(s):  
Hiroshi Matsushima ◽  
Taisuke Mori ◽  
Fumitake Ito ◽  
Takuro Yamamoto ◽  
Makoto Akiyama ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Receptor Alpha ◽  
Uterine Endometrial Cancer ◽  
Estrogen Related Receptor

Estrogen-related receptor alpha (ERRα) is required for PGC-1α-dependent gene expression in the mouse brain

Neuroscience ◽  
2021 ◽  
Author(s):  
L.J. McMeekin ◽  
K.L. Joyce ◽  
L.M. Jenkins ◽  
B.M. Bohannon ◽  
K.D. Patel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Brain ◽  
Receptor Alpha ◽  
Estrogen Related Receptor

scholarly journals Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening Assays

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 841 ◽  
Author(s):  
Caitlin Lynch ◽  
Jinghua Zhao ◽  
Srilatha Sakamuru ◽  
Li Zhang ◽  
Ruili Huang ◽  
...  
Keyword(s):  
Cancer Progression ◽  
High Throughput ◽  
High Throughput Screening ◽  
Biological Properties ◽  
Environmental Chemicals ◽  
Hek293 Cells ◽  
Peroxisome Proliferator ◽  
Receptor Alpha ◽  
Screening Assays ◽  
Estrogen Related Receptor

The nuclear receptor, estrogen-related receptor alpha (ERRα; NR3B1), plays a pivotal role in energy homeostasis. Its expression fluctuates with the demands of energy production in various tissues. When paired with the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), the PGC/ERR pathway regulates a host of genes that participate in metabolic signaling networks and in mitochondrial oxidative respiration. Unregulated overexpression of ERRα is found in many cancer cells, implicating a role in cancer progression and other metabolism-related diseases. Using high throughput screening assays, we screened the Tox21 10K compound library in stably transfected HEK293 cells containing either the ERRα-reporter or the reporter plus PGC-1α expression plasmid. We identified two groups of antagonists that were potent inhibitors of ERRα activity and/or the PGC/ERR pathway: nine antineoplastic agents and thirteen pesticides. Results were confirmed using gene expression studies. These findings suggest a novel mechanism of action on bioenergetics for five of the nine antineoplastic drugs. Nine of the thirteen pesticides, which have not been investigated previously for ERRα disrupting activity, were classified as such. In conclusion, we demonstrated that high-throughput screening assays can be used to reveal new biological properties of therapeutic and environmental chemicals, broadening our understanding of their modes of action.

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