Epgn, also known as epithelial mitogen, is an epidermal growth factor receptor (EGFR) ligand. As an EGFR ligand, it is involved in the EGFR signaling pathway, which regulates many crucial cellular programs. Different from some high-affinity EGFR ligands, Epgn is a low-affinity ligand [2]. It has significance in processes like cell differentiation and in maintaining the normal function of epithelial cells [1]. Genetic models can be used to study its function and the underlying molecular mechanisms.

Epgn was identified for the first time in granulosa cells as rapidly induced by LH/hCG and it initiates cumulus expansion, similar to other EGF-receptor ligands [6]. In a contact dermatitis model, curcumin inhibited the upregulation of Epgn by 2,4,6-trinitrochlorobenzene, and ear swelling induced by the chemical might be mediated, in part, by the EPGN-ERK proliferation pathway [4]. In a mucosal damage and fungal infection model, transcriptional profiling identified significant upregulation of Epgn upon mucosal damage, and treatment with recombinant human Epgn suppressed epithelial cell extrusion, leading to reduced fungal invasion [5]. In lung cancer pleural metastasis, the interaction between epithelial mitogen (EPGN) in mesothelial cells and EGFR in epithelial cells was supported through spatial distribution analysis, revealing their significant proximity and highlighting the role of this interaction in pleural metastasis [3].

In conclusion, Epgn plays important roles in multiple biological processes and disease conditions. Its functions in cumulus expansion, skin inflammation, mucosal defense against fungal invasion, and lung cancer pleural metastasis have been revealed through various in vivo studies. These findings from model-based research contribute to understanding its essential biological functions and offer potential targets for treatment in related diseases, especially in the area of cancer metastasis and inflammation-related skin diseases.

References:

1. Freed, Daniel M, Bessman, Nicholas J, Kiyatkin, Anatoly, Lidke, Diane S, Lemmon, Mark A. 2017. EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics. In Cell, 171, 683-695.e18. doi:10.1016/j.cell.2017.09.017. https://pubmed.ncbi.nlm.nih.gov/28988771/

2. Singh, Bhuminder, Carpenter, Graham, Coffey, Robert J. 2016. EGF receptor ligands: recent advances. In F1000Research, 5, . doi:10.12688/f1000research.9025.1. https://pubmed.ncbi.nlm.nih.gov/27635238/

3. Li, Pei-Heng, Zhang, Xin, Yan, Huayun, Li, Zhi-Hui, Shu, Yang. 2024. Contribution of crosstalk of mesothelial and tumoral epithelial cells in pleural metastasis of lung cancer. In Translational lung cancer research, 13, 965-985. doi:10.21037/tlcr-24-118. https://pubmed.ncbi.nlm.nih.gov/38854934/

4. Sakai, Hiroyasu, Sato, Ken, Sato, Fumiaki, Narita, Minoru, Chiba, Yoshihiko. 2017. Curcumin inhibits epigen and amphiregulin upregulated by 2,4,6-trinitrochlorobenzene associated with attenuation of skin swelling. In Inflammation research : official journal of the European Histamine Research Society ... [et al.], 66, 663-678. doi:10.1007/s00011-017-1048-0. https://pubmed.ncbi.nlm.nih.gov/28405735/

5. Wurster, Sebastian, Ruiz, Oscar E, Samms, Krystin M, Kontoyiannis, Dimitrios P, Eisenhoffer, George T. . EGF-mediated suppression of cell extrusion during mucosal damage attenuates opportunistic fungal invasion. In Cell reports, 34, 108896. doi:10.1016/j.celrep.2021.108896. https://pubmed.ncbi.nlm.nih.gov/33761358/

6. Carletti, Martha Z, Christenson, Lane K. 2009. Rapid effects of LH on gene expression in the mural granulosa cells of mouse periovulatory follicles. In Reproduction (Cambridge, England), 137, 843-55. doi:10.1530/REP-08-0457. https://pubmed.ncbi.nlm.nih.gov/19225042/