Prg2, also known as plasticity-related gene 2 or phospholipid phosphatase-related protein 3 (PLPPR3), is involved in multiple biological processes. In neurons, it is part of a growth program that controls axon morphogenesis. Prg2 interacts with PTEN, a phosphatase, and inhibits it to stabilize membrane PI(3,4,5)P3, thus enabling axon filopodia and branch formation [2,4]. In the immune system, the protein encoded by Prg2 mRNA is related to eosinophil-involved immune processes [3].

In a study on placenta previa and percreta, PRG2 protein levels were upregulated, and it was mislocalized in fetal membranes, suggesting it could be a marker for these conditions and might be associated with increased trophoblast invasiveness [1]. In a GWAS on white blood cell morphological parameters in Sardinians, a significant signal affecting eosinophil scatter fell within the Prg2 gene, and a rare mutation in Prg2 was found to potentially explain changes in eosinophil morphology [6]. In bullous pemphigoid treatment, dupilumab was associated with down-regulation of PRG2, which is involved in eosinophil activation [5]. In resistant CML cells, 5-Azacytidine re-expressed PRG2, inactivated STAT3, and increased sensitivity to imatinib, indicating PRG2 might be a tumor suppressor gene [7].

In conclusion, Prg2 has diverse functions in neuronal development, immune responses, and is associated with various disease conditions such as placenta-related disorders, eosinophil-related morphological changes, bullous pemphigoid, and CML. Studies, especially those using genetic models, have provided insights into its role in these biological processes and diseases, contributing to our understanding of the underlying mechanisms and potential therapeutic targets.

References:

1. Zhang, Elisa T, Hannibal, Roberta L, Badillo Rivera, Keyla M, Lyell, Deirdre J, Baker, Julie C. . PRG2 and AQPEP are misexpressed in fetal membranes in placenta previa and percreta†. In Biology of reproduction, 105, 244-257. doi:10.1093/biolre/ioab068. https://pubmed.ncbi.nlm.nih.gov/33982062/

2. Brosig, Annika, Fuchs, Joachim, Ipek, Fatih, Leondaritis, George, Eickholt, Britta J. . The Axonal Membrane Protein PRG2 Inhibits PTEN and Directs Growth to Branches. In Cell reports, 29, 2028-2040.e8. doi:10.1016/j.celrep.2019.10.039. https://pubmed.ncbi.nlm.nih.gov/31722215/

3. Qiao, Xiaoyue, Lu, Li, Zhou, Kangxing, Liang, Jun, Dou, Huan. 2022. The correlation between proteoglycan 2 and neuropsychiatric systemic lupus erythematosus. In Clinical immunology (Orlando, Fla.), 239, 109042. doi:10.1016/j.clim.2022.109042. https://pubmed.ncbi.nlm.nih.gov/35568106/

4. Fuchs, Joachim, Eickholt, Britta J, Leondaritis, George. 2020. Harnessing PTEN's Growth Potential in Neuronal Development and Disease. In Neuroscience insights, 15, 2633105520959056. doi:10.1177/2633105520959056. https://pubmed.ncbi.nlm.nih.gov/32974612/

5. Yan, Tianmeng, Xie, Yinghan, Liu, Yuhua, Zuo, Ya-Gang, Zhang, Zhenying. 2023. Dupilumab effectively and rapidly treats bullous pemphigoid by inhibiting the activities of multiple cell types. In Frontiers in immunology, 14, 1194088. doi:10.3389/fimmu.2023.1194088. https://pubmed.ncbi.nlm.nih.gov/37575240/

6. Marongiu, Michele, Pérez-Mejías, Gonzalo, Orrù, Valeria, Cucca, Francesco, Zoledziewska, Magdalena. . GWAS of genetic factors affecting white blood cell morphological parameters in Sardinians uncovers influence of chromosome 11 innate immunity gene cluster on eosinophil morphology. In Human molecular genetics, 32, 790-797. doi:10.1093/hmg/ddac238. https://pubmed.ncbi.nlm.nih.gov/36136759/

7. Al-Jamal, Hamid Ali Nagi, Johan, Muhammad Farid, Mat Jusoh, Siti Asmaa, Ismail, Imilia, Wan Taib, Wan Rohani. 2018. Re-Expression of Bone Marrow Proteoglycan-2 by 5-Azacytidine is associated with STAT3 Inactivation and Sensitivity Response to Imatinib in Resistant CML Cells. In Asian Pacific journal of cancer prevention : APJCP, 19, 1585-1590. doi:. https://pubmed.ncbi.nlm.nih.gov/29936783/