Egr3, also known as early growth response 3, is a transcription factor that plays crucial roles in various biological processes. It is involved in pathways related to mechanosensing, cell differentiation, and immune regulation. Genetic models, such as gene knockout mouse models, have been essential in uncovering its functions [1,2,3,4].

In zebrafish, Egr3 null mutants display a complete loss of cardiac valve leaflets, indicating its necessity in cardiac valve morphogenesis [1]. In mice, Egr3 deficiency leads to a lupus-like disease with dysregulated effector T-cell activation, suggesting its role in suppressing excessive immune responses [3]. Egr3-deficient mice also show alleviated cigarette smoke-induced pulmonary inflammation in a chronic obstructive pulmonary disease (COPD) model, as Egr3 deficiency suppresses the TLR4/NF-κB pathway and downregulates TIMP-1 expression [4]. In the uterine decidualization process in mice, Egr3 is an important regulator that targets Hand2 in response to progesterone/cAMP/HB-EGF pathway [2].

In conclusion, Egr3 is a key regulator in multiple biological processes. Gene knockout mouse models have been instrumental in revealing its functions in cardiac valve development, immune regulation, and COPD progression, among others. Understanding Egr3 provides insights into the underlying mechanisms of these biological processes and potential disease-related pathways, which may contribute to the development of new therapeutic strategies.

References:

1. da Silva, Agatha Ribeiro, Gunawan, Felix, Boezio, Giulia L M, Juan, Thomas, Stainier, Didier Y R. 2024. egr3 is a mechanosensitive transcription factor gene required for cardiac valve morphogenesis. In Science advances, 10, eadl0633. doi:10.1126/sciadv.adl0633. https://pubmed.ncbi.nlm.nih.gov/38748804/

2. Yue, Liang, Yu, Hai-Fan, Tian, Xue-Chao, Guo, Bin, Zheng, Lian-Wen. 2022. Egr3 as an important regulator of uterine decidualization through targeting Hand2. In Cell biology international, 47, 406-416. doi:10.1002/cbin.11933. https://pubmed.ncbi.nlm.nih.gov/36317452/

3. Morita, Kaoru, Okamura, Tomohisa, Sumitomo, Shuji, Fujio, Keishi, Yamamoto, Kazuhiko. . Emerging roles of Egr2 and Egr3 in the control of systemic autoimmunity. In Rheumatology (Oxford, England), 55, ii76-ii81. doi:. https://pubmed.ncbi.nlm.nih.gov/27856665/

4. Zhang, Fang, Geng, Yumei, Shi, Xuefeng, Duo, Jie. 2025. EGR3 deficiency alleviates cigarette smoke-induced pulmonary inflammation in COPD through TLR4/NF-κB/TIMP-1 axis. In Biochemical and biophysical research communications, 763, 151741. doi:10.1016/j.bbrc.2025.151741. https://pubmed.ncbi.nlm.nih.gov/40220490/