Scg2, also known as secretogranin II, is a member of the chromogranin family of acidic secretory proteins. It plays diverse roles in multiple biological processes. In the nervous system, it may be involved in neural circuit reorganization as FOS activates its transcription to coordinate changes in inhibition [4]. It is also related to angiogenesis, with its cleaved peptide secretoneurin stimulating ovarian angiogenesis after being induced in granulosa cells by hCG [5].

In disease-related research, in traumatic brain injury (TBI) mouse models, astrocytic Scg2 knockout in the frontal cortex reduced blood-brain barrier (BBB) damage, mitigated inflammation, and inhibited schizophrenia-like behaviors. Scg2 was found to trigger BBB disruption via the CypA-MMP-9 signaling pathway [1]. In colorectal cancer, CRC cell lines with Scg2 knockdown have reduced invasive, proliferative, and proliferative capacity. High Scg2 expression was considered a risky factor predicting poorer prognosis and the high-expression subgroup was more suitable for immunotherapy [2]. In head and neck squamous cell carcinoma (HNSCC), knocking down Scg2 reduced the proliferation and migration of HNSCC cells and disrupted M2 macrophage polarization [3].

In conclusion, Scg2 is involved in various biological functions such as neural circuit regulation and angiogenesis. Gene knockout models in mice have revealed its significance in diseases like TBI-related psychiatric disorders, colorectal cancer, and HNSCC, providing potential therapeutic targets for these conditions.

References:

1. Lin, Chao, Zhao, Pengzhang, Sun, Guangchi, Liu, Ning, Ji, Jing. . SCG2 mediates blood-brain barrier dysfunction and schizophrenia-like behaviors after traumatic brain injury. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 38, e70016. doi:10.1096/fj.202401117R. https://pubmed.ncbi.nlm.nih.gov/39225388/

2. Weng, Siyuan, Liu, Zaoqu, Ren, Xiaofeng, Deng, Jinhai, Han, Xinwei. 2022. SCG2: A Prognostic Marker That Pinpoints Chemotherapy and Immunotherapy in Colorectal Cancer. In Frontiers in immunology, 13, 873871. doi:10.3389/fimmu.2022.873871. https://pubmed.ncbi.nlm.nih.gov/35844556/

3. Miao, Cheng, You, Xiaotong, Zhang, Zijian, Li, Longjiang, Pan, Jian. 2024. SCG2 Mediates HNSCC Progression With CCL2/TGFβ1high M2 Macrophage Infiltration. In Oral diseases, 31, 782-795. doi:10.1111/odi.15154. https://pubmed.ncbi.nlm.nih.gov/39404611/

4. Yap, Ee-Lynn, Pettit, Noah L, Davis, Christopher P, Harvey, Christopher D, Greenberg, Michael E. 2020. Bidirectional perisomatic inhibitory plasticity of a Fos neuronal network. In Nature, 590, 115-121. doi:10.1038/s41586-020-3031-0. https://pubmed.ncbi.nlm.nih.gov/33299180/

5. Hannon, Patrick R, Duffy, Diane M, Rosewell, Katherine L, Akin, James W, Curry, Thomas E. . Ovulatory Induction of SCG2 in Human, Nonhuman Primate, and Rodent Granulosa Cells Stimulates Ovarian Angiogenesis. In Endocrinology, 159, 2447-2458. doi:10.1210/en.2018-00020. https://pubmed.ncbi.nlm.nih.gov/29648638/