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JANUARY 19, 2021 // -- In a recent study published in the international journal Science Advances, scientists from the Westa Institute and others in the United States found that a protein that turns on and off the expression of special genes during blood cell development, EGR1 (Early Growth Response Factor 1, Early Response 1), or inhibits the expression of inflammatory genes in macrophages.
As part of the body's ability to protect against pathogens, macrophages play an important role in the initiation, maintenance and receding of inflammation, and the results may help scientists gain a deeper understanding of how macrophages are activated and insulate in inflammation, which is important for many of the body's normal and pathological conditions.
Image source: Professor Alessandro Gardini, a researcher at The Wistar Institute, says that by understanding the role of EGR1 in depth, we can shed light on the basic processes of macrophage maturation, which is necessary for many of the body's immune responses, including inflammatory processes;
macrophages are a special class of immune cells, which can eliminate foreign pathogens, cell fragments and cancer cells, and its multi-step maturation process from the primary cells of bone marrow requires the coordination of key transcription factors to regulate the expression of specific genes, EGR1 is one of the factors, but its function is not clear at present.
In order to respond to tissue damage and infection, monocytes in the immune system leave the blood-soaked tissue, where they undergo fine developmental processes and mature into macrophages that have the ability to devour pathogens, promote inflammation and trigger pathogen-specific immune responses.
Currently, researchers have not fully clarified the molecular mechanisms behind macrophage maturation, and the same set of transcription factors that play a role in early monocyte development are thought to be associated with the transition of monocytes to macrophages. In the
article, researcher Gardini and colleagues used a new model to reproduce the differentiation process from monocytes to macrophages in-body, as well as a systematic genomic analysis of the role of EGR1 in the process;
Previous studies, researchers have revealed that EGR1 regulates the molecular mechanisms of gene expression in monocytes and macrophages by interacting with enhancers, a class of short-chain regulatory DNA sequences that can be combined by specific transcription factors to enhance the expression of related genes.
study, researchers found that EGR1 inhibits the function of inflammatory enhancers in developing and mature macrophages, thereby impairing their activity and immune response. Avery Zucco, a researcher at
, said the results suggest that EGR1 may play a far more important role in regulating inflammation in the body than it plays in the development of blood cells, and is directly related to the control of inflammation in the body in human health and disease conditions.
original source: Marco Trizzino, Avery Zucco, Sandra Deliard, et al. EGR1 is a gatekeeper of inflammatory enhancers in human macrophages, Science Advances13 Jan 2021:Vol. 7, no. 3, eaaz8836 DOI:10.1126/sciadv.aaz8836