Sema7a, belonging to the Semaphorin family, is a highly glycosylated protein with five glycosylated sites. It is involved in multiple biological processes such as axonal guidance, immune regulation, and metabolism. Sema7a has been implicated in various pathways including integrin-related signaling, which is essential for fibroblast behaviors during wound healing [1,4]. It also plays a role in regulating macrophage metabolic remodeling related to inflammation resolution [3].

In obesity and hepatic steatosis, Sema7a -/- mice exhibited aggravated high-fat diet (HFD)-induced obesity, enhanced adipogenesis in adipose-derived mesenchymal stem cells, increased hepatic steatosis, and insulin resistance. In contrast, administration of recombinant Sema7A protected against diet-induced obesity, suggesting an inhibitory role of Sema7a in these metabolic conditions [2]. In inflammatory peritonitis, SEMA7A -/- animals had increased inflammation compared to wild-type animals, highlighting its protective role in this inflammatory process [6]. In the olfactory system, Sema7A or PlxnC1 knockout mice showed perturbed initiation of synapse formation and dendrite selection in mitral/tufted cells, indicating its importance in activity-dependent olfactory synapse formation [5].

In conclusion, Sema7a plays crucial roles in multiple biological processes. Gene knockout mouse models have revealed its functions in obesity, hepatic steatosis, inflammatory peritonitis, and olfactory synapse formation. These findings suggest Sema7a could be a potential therapeutic target for related diseases such as obesity, metabolic diseases, and inflammatory disorders [2,3,5,6].

References:

1. Liu, Zhonglong, Meng, Xiaoyan, Zhang, Yuxin, Liu, Liu, He, Yue. 2024. FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression. In International journal of oral science, 16, 26. doi:10.1038/s41368-024-00289-w. https://pubmed.ncbi.nlm.nih.gov/38548747/

2. Lu, Qiongyu, Liu, Ziting, Zhao, Luyao, Tang, Chaojun, Zhu, Li. 2023. Sema7A protects against high-fat diet-induced obesity and hepatic steatosis by regulating adipo/lipogenesis. In Molecular metabolism, 70, 101698. doi:10.1016/j.molmet.2023.101698. https://pubmed.ncbi.nlm.nih.gov/36842496/

3. Körner, Andreas, Bernard, Alice, Fitzgerald, Julia C, Giera, Martin, Mirakaj, Valbona. . Sema7A is crucial for resolution of severe inflammation. In Proceedings of the National Academy of Sciences of the United States of America, 118, . doi:10.1073/pnas.2017527118. https://pubmed.ncbi.nlm.nih.gov/33637648/

4. Hu, Ping, Miller, Andrew E, Yeh, Chiuan-Ren, Civelek, Mete, Barker, Thomas H. 2023. SEMA7a primes integrin α5β1 engagement instructing fibroblast mechanotransduction, phenotype and transcriptional programming. In Matrix biology : journal of the International Society for Matrix Biology, 121, 179-193. doi:10.1016/j.matbio.2023.06.006. https://pubmed.ncbi.nlm.nih.gov/37422024/

5. Inoue, Nobuko, Nishizumi, Hirofumi, Naritsuka, Hiromi, Kiyonari, Hiroshi, Sakano, Hitoshi. 2018. Sema7A/PlxnCl signaling triggers activity-dependent olfactory synapse formation. In Nature communications, 9, 1842. doi:10.1038/s41467-018-04239-z. https://pubmed.ncbi.nlm.nih.gov/29743476/

6. Körner, Andreas, Köhler, David, Schneider, Mariella, Mirakaj, Valbona, Rosenberger, Peter. 2023. Semaphorin 7A is protective during inflammatory peritonitis through integrin receptor signaling. In Frontiers in immunology, 14, 1251026. doi:10.3389/fimmu.2023.1251026. https://pubmed.ncbi.nlm.nih.gov/38094294/