
-   EGR2 was significantly elevated in myelin-reactive CD4+ T cells from patients with multiple sclerosis and mice with autoimmune neuroinflammation. EGR2 enhanced TH17 cell differentiation and myeloid cell recruitment to the central nervous system (CNS) by upregulating pathogenesis-associated genes and myelomonocytic chemokines. T cell-specific deletion of Egr2 attenuated neuroinflammation without compromising the host's ability to control infections [PMID: 37443284].
-   EGR2 plays a key role in the PTEN-induced apoptotic pathway. EGR2 could induce apoptosis in a large proportion of cancer cell lines by altering the permeability of mitochondrial membranes, releasing cytochrome c and activating caspase-3, -8, and -9. EGR2 directly transactivates expression of BNIP3L and BAK [PMID: 12687019]. Expression of EGR2 was decreased in ovarian tumors compared with corresponding normal tissues. Colony-formation assays indicated that EGR2 was able to suppress growth of cancer cells and knockdown of EGR2 accelerated cell growth [PMID: 11494141].
-   EGR2 expression is a selective property of alveolar macrophages in the lung. EGR2 is driven by TGF-beta and GM-CSF in a PPAR-gamma-dependent manner to control alveolar macrophage differentiation. EGR2 is required for repopulation of the alveolar niche after sterile, bleomycin-induced lung injury and demonstrate that EGR2-dependent, monocyte-derived alveolar macrophages are vital for effective tissue repair after injury [PMID: 34797692].
-   Decreased expression of Egr2 (KROX20) was observed in aortic valves of patients with defective aortic valves (AoVs) disease. Krox20 knockout mice had features of human AoV disease, including excess of proteoglycan deposition and reduction of collagen fibers. Loss of Krox20 results in aortic valve regurgitation and impaired transcriptional activation of fibrillar collagen genes. Krox20-mediated activation of fibrillar Col1a1 and Col3a1 genes is crucial to avoid postnatal degeneration of the AoV leaflets [PMID: 25344368].
-   Transcription factors Early Growth Response 2 (EGR2) was highly induced in tumour infiltrating T cells (TILs) in tumors from cohorts of colorectal, liver and lung cancer patients. Deficiency of Egr2 and 3 in T cells resulted in enhanced tumour growth and fewer TILs in mouse models. Thus, Egr2 is important for maintaining anti-tumour responses of exhausted CD8 + TILs [PMID: 36342511].

## Summary

EGR2 encodes a zinc finger transcription factor involved in various cellular processes including Schwann cell myelination and hindbrain segmentation [CS: 10]. EGR2 regulates gene expression related to cell differentiation, myelin formation, and apoptosis, often in response to tissue damage or inflammation [CS: 9]. This protein's activity includes the direct transactivation of genes such as BNIP3L and BAK, which are involved in the apoptotic pathway by mediating mitochondrial membrane permeability and caspase activation [CS: 7]. In addition to that, EGR2's role in the liver involves the induction of genes that produce collagen, an essential component for restoring the structural integrity of liver tissue after toxic injury [CS: 6]. Its activation promotes liver tissue remodeling, effectively repairing and sealing damaged areas, and mitigating the adverse effects of toxins on liver function [CS: 6].

The increase in EGR2 expression in response to infection, such as with Toxoplasma gondii, is connected to an augmented immune response, possibly through the upregulation of immune cell recruitment markers [CS: 5]. This suggests that EGR2's role in elevating expression of genes related to immune cell presence is a mechanism to enhance the liver's resilience against pathogen-related damage [CS: 5]. In contrast, in liver fibrosis, a condition marked by excessive tissue scarring, instead of serving a protective role, EGR2 upregulation contributes to the pathological process [CS: 6]. RNA silencing studies reveal that EGR2 may drive the amplification of fibrogenic gene expression, as silencing EGR2 leads to decreased collagen-associated mRNA levels like Col1a1 and, consequently, less collagen deposition [CS: 7]. This suggests that in the stressed liver, upregulated EGR2 could intensify fibrosis by promoting expression of extracellular matrix components [CS: 7].
