Researchers at Karolinska Institutet have discovered a protein that is crucial in mediating the anti-inflammatory actions of nuclear lipid receptors. The study identified GPS2, a protein that directly interacts with receptors, as a central component of a protein network, or a “genomic positioning system.”
The findings are published in Genes & Development in a paper titled “GPS2-dependent corepressor/SUMO pathways govern anti-inflammatory actions of LRH-1 and LXRβ in the hepatic acute phase response.”
Numerous nuclear receptors are known as master regulators of lipid metabolism and homeostasis. Recent research indicates that these receptors also play important roles in the control of inflammation, but the mechanisms had not been revealed.
Eckardt Treuter, Ph.D., and his team set out to elucidate this pathway. They specifically studied how the nuclear lipid receptors LRH-1 and LXR inhibit inflammatory gene expression in the liver during the acute phase response.
The investigators observed that GPS2 was a crucial part of this network. It determines where and when these lipid receptors can control anti-inflammatory processes.
The identified pathway connects metabolism and inflammation and is therefore relevant for the understanding of metabolic diseases such as diabetes and atherosclerosis. The researchers suspect even broader roles of related pathways in different tissues linked to metabolic diseases and to cancers.
“We are now closer to understanding at the molecular level how dys-regulation of individual components of these pathways causes alterations in gene expression that contribute to the development of metabolic diseases linked to inflammation,” Dr. Treuter remarks. “This knowledge may open up novel pharmacological interventions. For example, drugs that stabilize receptor interactions with GPS2 could possibly trigger the anti-inflammatory pathway.”