Selplg-KO Mouse

SELPLG, also known as selectin P ligand gene, encodes P-selectin glycoprotein ligand 1 (PSGL-1). PSGL-1 is part of a receptor/ligand complex with P-selectin, involved in processes like lymphocyte recruitment, cell migration, and chemotaxis, which are crucial in inflammation, immune response, and the development of atherosclerosis [3,4,5,6].

In osteosarcoma, lnc-SELPLG-2:1, an isoform, acts as an oncogenesis activator. Its overexpression promotes cell proliferation, migration, and invasion, while its inhibition accelerates apoptosis. This occurs via the hsa-miR-10a-5p/BTRC cascade, where lnc-SELPLG-2:1 competitively binds to hsa-miR-10a-5p, preventing BTRC degradation and activating related proteins [1]. In acute respiratory distress syndrome (ARDS), SELPLG lung tissue expression increases in response to LPS-and ventilator-induced lung injury. A recombinant tandem PSGL1 immunoglobulin fusion molecule can decrease SELPLG expression and protect from lung injury. The SELPLG promoter is regulated by hypoxia-inducible transcription factors and NRF2, and DNA methylation also affects its expression [2].

In summary, SELPLG is vital in processes like immune cell recruitment and cell migration. Studies, including those on osteosarcoma and ARDS, demonstrate its significance in disease-related biological functions. These findings from various disease models help in understanding how SELPLG dysregulation contributes to disease development, potentially guiding future therapeutic strategies.

References:

1. Li, Shiyuan, Zeng, Ming, Yang, Lin, Kuang, Manyuan, Li, Jiaying. 2022. Lnc-SELPLG-2:1 enhanced osteosarcoma oncogenesis via hsa-miR-10a-5p and the BTRC cascade. In BMC cancer, 22, 1044. doi:10.1186/s12885-022-10040-5. https://pubmed.ncbi.nlm.nih.gov/36199080/

2. Sun, Xiaoguang, Sammani, Saad, Hufford, Matthew, Garcia, Joe G N, Bime, Christian. 2023. Targeting SELPLG/P-selectin glycoprotein ligand 1 in preclinical ARDS: Genetic and epigenetic regulation of the SELPLG promoter. In Pulmonary circulation, 13, e12206. doi:10.1002/pul2.12206. https://pubmed.ncbi.nlm.nih.gov/36873461/

3. Fenoglio, Chiara, Galimberti, Daniela, Ban, Maria, Compston, Alastair, Sawcer, Stephen. 2005. SELPLG and SELP single-nucleotide polymorphisms in multiple sclerosis. In Neuroscience letters, 394, 92-6. doi:. https://pubmed.ncbi.nlm.nih.gov/16257118/

4. Tregouet, D A, Barbaux, S, Poirier, O, Cambien, F, Tiret, L. . SELPLG gene polymorphisms in relation to plasma SELPLG levels and coronary artery disease. In Annals of human genetics, 67, 504-11. doi:. https://pubmed.ncbi.nlm.nih.gov/14641238/

5. Volcik, Kelly A, Catellier, Diane, Folsom, Aaron R, Wasserman, Bruce, Boerwinkle, Eric. 2009. SELP and SELPLG genetic variation is associated with cell surface measures of SELP and SELPLG: the Atherosclerosis Risk in Communities Carotid MRI Study. In Clinical chemistry, 55, 1076-82. doi:10.1373/clinchem.2008.119487. https://pubmed.ncbi.nlm.nih.gov/19395438/

6. Luan, Shi-Lu, Boulanger, Emmanuelle, Ye, Hongtao, Isaacson, Peter G, Du, Ming-Qing. . Primary effusion lymphoma: genomic profiling revealed amplification of SELPLG and CORO1C encoding for proteins important for cell migration. In The Journal of pathology, 222, 166-79. doi:10.1002/path.2752. https://pubmed.ncbi.nlm.nih.gov/20690162/