Epor, short for erythropoietin receptor, is a member of the cytokine class I receptor family. It classically mediates erythropoietin (EPO)-induced erythroblast proliferation and differentiation, thus being crucial for erythropoiesis [1]. Additionally, it has been implicated in various other biological processes through associated signaling pathways, such as the Jak2-p27Kip1 pathway which impacts erythroid progenitor proliferation [1]. Genetic models like EpoR-tdTomato-Cre mice are valuable tools for studying Epor expression and function [3].

In in vivo studies using KO/CKO mouse models, deletion of Epor in osteoprogenitor cells (EpoR:Osx-cre, cKO) increased vertebral bone volume in female mice, indicating its role in bone homeostasis and Epo-induced bone loss [4]. In the monocytic lineage, conditional deletion of Epor in LysMCre model mice reduced the increase in bone marrow preosteoclasts and resulting bone loss after high-dose EPO administration, suggesting EPOR in this lineage contributes to EPO-driven effects on bone mass [2]. Myeloid-specific EPOR-deficient mice showed restrained M2 macrophage polarization and impaired inflammation resolution in acute lung injury, highlighting its role in macrophage polarization [5].

In conclusion, Epor is essential for erythropoiesis and also plays significant roles in bone homeostasis, macrophage polarization and potentially other biological processes. The use of Epor KO/CKO mouse models has provided key insights into its functions in bone-related diseases and acute lung injury, enhancing our understanding of these disease mechanisms and potentially paving the way for new therapeutic strategies.

References:

1. Pegka, Fragka, Ben-Califa, Nathalie, Neumann, Drorit, Jäkel, Heidelinde, Hengst, Ludger. 2023. EpoR Activation Stimulates Erythroid Precursor Proliferation by Inducing Phosphorylation of Tyrosine-88 of the CDK-Inhibitor p27Kip1. In Cells, 12, . doi:10.3390/cells12131704. https://pubmed.ncbi.nlm.nih.gov/37443738/

2. Awida, Zamzam, Hiram-Bab, Sahar, Bachar, Almog, Gabet, Yankel, Neumann, Drorit. 2022. Erythropoietin Receptor (EPOR) Signaling in the Osteoclast Lineage Contributes to EPO-Induced Bone Loss in Mice. In International journal of molecular sciences, 23, . doi:10.3390/ijms231912051. https://pubmed.ncbi.nlm.nih.gov/36233351/

3. Zhang, Huan, Wang, Shihui, Liu, Donghao, Chen, Lixiang, An, Xiuli. . EpoR-tdTomato-Cre mice enable identification of EpoR expression in subsets of tissue macrophages and hematopoietic cells. In Blood, 138, 1986-1997. doi:10.1182/blood.2021011410. https://pubmed.ncbi.nlm.nih.gov/34098576/

4. Rauner, Martina, Murray, Marta, Thiele, Sylvia, Hofbauer, Lorenz C, Wielockx, Ben. 2021. Epo/EpoR signaling in osteoprogenitor cells is essential for bone homeostasis and Epo-induced bone loss. In Bone research, 9, 42. doi:10.1038/s41413-021-00157-x. https://pubmed.ncbi.nlm.nih.gov/34518518/

5. Zhang, Wen, Wang, Yao, Li, Chuanwei, He, Binfeng, Wang, Guansong. 2021. Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury. In Frontiers in immunology, 12, 768435. doi:10.3389/fimmu.2021.768435. https://pubmed.ncbi.nlm.nih.gov/34925338/

6. Zhang, Yajing, Wang, Senyu, Han, Songtao, Feng, Yangchun. 2022. Pan-Cancer Analysis Based on EPOR Expression With Potential Value in Prognosis and Tumor Immunity in 33 Tumors. In Frontiers in oncology, 12, 844794. doi:10.3389/fonc.2022.844794. https://pubmed.ncbi.nlm.nih.gov/35359375/