Scrg1, or scrapie responsive gene 1, encodes a highly conserved, cysteine-rich protein mainly expressed in the central nervous system, targeted to the Golgi apparatus and large dense-core vesicles/secretory granules in neurons [3,5,9]. It may be involved in the host response to stress and neuronal cell death, potentially related to autophagy [3,5]. Also, it is associated with several signaling pathways, like the MAPK pathway in macrophages [4].

In liver-related diseases, knockdown of linc-SCRG1 (a 3118-bp lncRNA) significantly reversed the effects of TGF-β1 on LX2 cells, such as inhibiting activation, promoting apoptosis, reducing proliferation, lessening invasion, and down-regulating fibrosis-related genes, suggesting its role in accelerating liver fibrosis [1]. In hepatocellular carcinoma, linc-SCRG1 acts as a ceRNA of miR26a to derepress SKP2, inducing the proliferation and migration of HCC cells [6]. In synovial inflammation, SCRG1 may be a potential therapeutic target and diagnostic marker for osteoarthritis, co-regulating immune-related pathways [2]. In macrophages, SCRG1 suppresses LPS-induced CCL22 production through ERK1/2 activation [4]. In mesenchymal stem cells, the SCRG1/BST1 axis regulates self-renewal, migration, and osteogenic differentiation potential [7,8].

In conclusion, Scrg1 has diverse functions in multiple biological processes and disease conditions. Its role in liver fibrosis, hepatocellular carcinoma, synovial inflammation, macrophage-mediated inflammation, and stem cell regulation is significant. Studies on Scrg1, especially through loss-of-function experiments, contribute to understanding disease mechanisms and may offer potential therapeutic strategies for related diseases.

References:

1. Wu, Jun-Cheng, Luo, Sheng-Zheng, Liu, Ting, Lu, Lun-Gen, Xu, Ming-Yi. 2018. linc-SCRG1 accelerates liver fibrosis by decreasing RNA-binding protein tristetraprolin. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33, 2105-2115. doi:10.1096/fj.201800098RR. https://pubmed.ncbi.nlm.nih.gov/30226813/

2. Liu, Guoqiang, He, Guisong, Zhang, Jie, Zhang, Zhongmin, Wang, Liang. 2022. Identification of SCRG1 as a Potential Therapeutic Target for Human Synovial Inflammation. In Frontiers in immunology, 13, 893301. doi:10.3389/fimmu.2022.893301. https://pubmed.ncbi.nlm.nih.gov/35720295/

3. Dron, Michel, Bailly, Yannick, Beringue, Vincent, Laude, Hubert, Dandoy-Dron, Françoise. 2006. SCRG1, a potential marker of autophagy in transmissible spongiform encephalopathies. In Autophagy, 2, 58-60. doi:. https://pubmed.ncbi.nlm.nih.gov/16874033/

4. Inoue, Manabu, Yamada, Junko, Aomatsu-Kikuchi, Emiko, Ishisaki, Akira, Chosa, Naoyuki. 2017. SCRG1 suppresses LPS-induced CCL22 production through ERK1/2 activation in mouse macrophage Raw264.7 cells. In Molecular medicine reports, 15, 4069-4076. doi:10.3892/mmr.2017.6492. https://pubmed.ncbi.nlm.nih.gov/28440453/

5. Dron, Michel, Bailly, Yannick, Beringue, Vincent, Laude, Hubert, Dandoy-Dron, Françoise. . Scrg1 is induced in TSE and brain injuries, and associated with autophagy. In The European journal of neuroscience, 22, 133-46. doi:. https://pubmed.ncbi.nlm.nih.gov/16029203/

6. Hu, Jun-Jie, Zhou, Cui, Luo, Xin, Xu, Zi-Xin, Xu, Ming-Yi. 2021. Linc-SCRG1 accelerates progression of hepatocellular carcinoma as a ceRNA of miR26a to derepress SKP2. In Journal of experimental & clinical cancer research : CR, 40, 26. doi:10.1186/s13046-020-01825-2. https://pubmed.ncbi.nlm.nih.gov/33422101/

7. Chosa, Naoyuki, Ishisaki, Akira. 2017. Two novel mechanisms for maintenance of stemness in mesenchymal stem cells: SCRG1/BST1 axis and cell-cell adhesion through N-cadherin. In The Japanese dental science review, 54, 37-44. doi:10.1016/j.jdsr.2017.10.001. https://pubmed.ncbi.nlm.nih.gov/29629000/

8. Aomatsu, Emiko, Takahashi, Noriko, Sawada, Shunsuke, Ishisaki, Akira, Chosa, Naoyuki. 2014. Novel SCRG1/BST1 axis regulates self-renewal, migration, and osteogenic differentiation potential in mesenchymal stem cells. In Scientific reports, 4, 3652. doi:10.1038/srep03652. https://pubmed.ncbi.nlm.nih.gov/24413464/

9. Dandoy-Dron, Françoise, Griffond, Bernadette, Mishal, Zohar, Tovey, Michael G, Dron, Michel. . Scrg1, a novel protein of the CNS is targeted to the large dense-core vesicles in neuronal cells. In The European journal of neuroscience, 18, 2449-59. doi:. https://pubmed.ncbi.nlm.nih.gov/14622145/