Srgn, also known as serglycin, is a proteoglycan gene expressed in immune cells. It is involved in multiple biological processes and associated with various disease-related pathways. For example, it may be involved in cell-cell interactions, inflammation, and tumor-related processes [1-10]. Gene knockout (KO) models have been valuable in studying its function.

In ischemic stroke models, Srgn KO mice showed reduced microglia-mediated neuroinflammation and alleviated ischemic brain injury, indicating that Srgn amplification exacerbates such injury by promoting microglial pro-inflammatory activation via the NF-κB signal pathway and increasing glycolysis in microglia [1]. In TTF-1-negative lung adenocarcinomas, Srgn overexpression was associated with a poor outcome, and in osteoarthritis, Srgn promoted macrophage recruitment through CCL3 regulation [2,3]. In endothelial cells, low shear stress enhanced Srgn expression via the PKA/CREB-dependent signaling pathway, and it may be involved in atherosclerotic plaque formation [4]. In breast cancer, Srgn overexpression was linked to chemoresistance, and in nasopharyngeal carcinoma, STAT3 regulated Srgn to promote tumor growth and metastasis [5,6]. In colorectal cancer, Srgn promoted metastasis as a downstream target of HIF-1α, and in triple-negative breast cancer, it formed a regulatory loop with TGFβ2 to confer invasion and metastasis [7,8]. In hepatocellular carcinoma, Srgn overexpression predicted poor prognosis, and in skin cutaneous melanoma, it was associated with patient survival and immune infiltrates [9,10].

In conclusion, Srgn is involved in a wide range of biological processes and disease conditions. The use of Srgn KO mouse models has been crucial in revealing its role in ischemic stroke, multiple types of cancers, osteoarthritis, and atherosclerosis. Understanding Srgn's functions provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Qian, Yi, Yang, Lixuan, Chen, Jian, Chen, Yan, Xu, Yun. 2024. SRGN amplifies microglia-mediated neuroinflammation and exacerbates ischemic brain injury. In Journal of neuroinflammation, 21, 35. doi:10.1186/s12974-024-03026-6. https://pubmed.ncbi.nlm.nih.gov/38287411/

2. Tanaka, Ichidai, Dayde, Delphine, Tai, Mei Chee, Hanash, Samir, Taguchi, Ayumu. . SRGN-Triggered Aggressive and Immunosuppressive Phenotype in a Subset of TTF-1-Negative Lung Adenocarcinomas. In Journal of the National Cancer Institute, 114, 290-301. doi:10.1093/jnci/djab183. https://pubmed.ncbi.nlm.nih.gov/34524427/

3. Zhang, Yi, Li, Zihua, Chen, Cheng, Li, Bing, Yang, Yunfeng. 2024. SRGN promotes macrophage recruitment through CCL3 in osteoarthritis. In Connective tissue research, 65, 330-342. doi:10.1080/03008207.2024.2380313. https://pubmed.ncbi.nlm.nih.gov/39067006/

4. Ma, Qinfeng, Gu, Wei, Li, Tianhan, Qiu, Juhui, Wang, Guixue. 2020. SRGN, a new identified shear-stress-responsive gene in endothelial cells. In Molecular and cellular biochemistry, 474, 15-26. doi:10.1007/s11010-020-03830-7. https://pubmed.ncbi.nlm.nih.gov/32712749/

5. Zhang, Zhijie, Qiu, Ni, Yin, Jiang, Liu, Jinbao, Zheng, Guopei. 2020. SRGN crosstalks with YAP to maintain chemoresistance and stemness in breast cancer cells by modulating HDAC2 expression. In Theranostics, 10, 4290-4307. doi:10.7150/thno.41008. https://pubmed.ncbi.nlm.nih.gov/32292495/

6. Wang, Yong-Li, Ren, Dan, Lu, Jin-Long, Liu, Fei, Qu, Shen-Hong. 2022. STAT3 regulates SRGN and promotes metastasis of nasopharyngeal carcinoma through the FoxO1-miR-148a-5p-CREB1 axis. In Laboratory investigation; a journal of technical methods and pathology, 102, 919-934. doi:10.1038/s41374-022-00733-7. https://pubmed.ncbi.nlm.nih.gov/35562411/

7. Xu, Yang, Xu, Jie, Yang, Yanfang, Li, Xubin, Zhao, Weipeng. 2018. SRGN Promotes Colorectal Cancer Metastasis as a Critical Downstream Target of HIF-1α. In Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 48, 2429-2440. doi:10.1159/000492657. https://pubmed.ncbi.nlm.nih.gov/30121667/

8. Zhang, Z, Deng, Y, Zheng, G, Gu, Y, He, Z. 2017. SRGN-TGFβ2 regulatory loop confers invasion and metastasis in triple-negative breast cancer. In Oncogenesis, 6, e360. doi:10.1038/oncsis.2017.53. https://pubmed.ncbi.nlm.nih.gov/28692037/

9. He, Lu, Zhou, Xinke, Qu, Chen, Zhang, Qiong, Hong, Jian. 2013. Serglycin (SRGN) overexpression predicts poor prognosis in hepatocellular carcinoma patients. In Medical oncology (Northwood, London, England), 30, 707. doi:10.1007/s12032-013-0707-4. https://pubmed.ncbi.nlm.nih.gov/23996242/

10. Wang, Xiaofang, Xiong, Hui, Liang, Daning, Li, Xiqing, Zhang, Kun. 2020. The role of SRGN in the survival and immune infiltrates of skin cutaneous melanoma (SKCM) and SKCM-metastasis patients. In BMC cancer, 20, 378. doi:10.1186/s12885-020-06849-7. https://pubmed.ncbi.nlm.nih.gov/32370744/