SRGN,也称为Serglycin,是一种硫酸软骨素蛋白聚糖,在多种免疫细胞中高度表达,包括巨噬细胞、自然杀伤细胞、树突状细胞、T细胞和B细胞。SRGN具有广泛的生物学功能,包括调节细胞粘附、迁移、增殖和免疫反应。SRGN在多种疾病中发挥重要作用,包括缺血性脑损伤、动脉粥样硬化、非酒精性脂肪性肝炎、肺癌、结直肠癌、乳腺癌和鼻咽癌。
在缺血性脑损伤中,SRGN在缺血性小鼠脑中显著上调,尤其是在巨噬细胞中。SRGN可以增强NF-κB信号通路和糖酵解途径的激活,促进巨噬细胞的促炎反应,从而加剧缺血性脑损伤和神经炎症[1]。此外,SRGN还可以通过CD44受体介导的信号通路影响血管内皮细胞的增殖和一氧化氮的产生,参与动脉粥样硬化的发生和发展[2]。
在非酒精性脂肪性肝炎中,SRGN在脂肪组织中高度表达,并与肥胖诱导的脂肪组织炎症相关。SRGN可以通过调节巨噬细胞的浸润和极化,影响脂肪组织的炎症反应和脂肪细胞的分化[4]。
在肺癌中,SRGN在TTF-1阴性肺癌细胞中显著过表达,并与其预后不良相关。SRGN可以促进PD-L1的表达和肿瘤浸润性免疫细胞(如CD8+ T细胞)的浸润,从而创造一个免疫抑制的肿瘤微环境,促进肿瘤的侵袭和转移[3]。此外,SRGN还可以通过激活CD44/CREB1信号通路,促进TGFβ2的表达和上皮-间质转化,从而促进三阴性乳腺癌的侵袭和转移[6]。
在结直肠癌中,SRGN在肿瘤组织中显著过表达,并与其预后不良相关。SRGN可以促进HIF-1α的表达,并通过激活PKA/CREB信号通路,促进肿瘤细胞的迁移和侵袭[5]。此外,SRGN还可以通过激活YAP转录因子,促进HDAC2的表达,从而维持肿瘤细胞的干性和化疗耐药性[9]。
在鼻咽癌中,SRGN与预后不良相关,并通过STAT3-FoxO1-miR-148a-5p-CREB1信号通路,促进肿瘤细胞的增殖、迁移和侵袭[7]。
此外,SRGN还可以作为心房颤动和心力衰竭的潜在生物标志物。SRGN在心房颤动和心力衰竭患者中显著上调,并与中性粒细胞和CD4+ T细胞的浸润相关[8]。
综上所述,SRGN是一种重要的蛋白聚糖,在多种疾病中发挥重要作用。SRGN可以通过多种信号通路,影响免疫细胞的功能、肿瘤细胞的侵袭和转移、以及血管内皮细胞的增殖和炎症反应。SRGN的研究有助于深入理解疾病的发生和发展机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
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. 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/
3. 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/
4. Doncheva, Atanaska I, Norheim, Frode A, Hjorth, Marit, Pejler, Gunnar, Kolset, Svein O. 2021. Serglycin Is Involved in Adipose Tissue Inflammation in Obesity. In Journal of immunology (Baltimore, Md. : 1950), 208, 121-132. doi:10.4049/jimmunol.2100231. https://pubmed.ncbi.nlm.nih.gov/34872979/
5. 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/
6. 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/
7. 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/
8. Zhang, Zhijun, Ding, Jianying, Mi, Xiaolong, Zhao, Bingye, Li, Xuewen. 2024. Identification of common mechanisms and biomarkers of atrial fibrillation and heart failure based on machine learning. In ESC heart failure, 11, 2323-2333. doi:10.1002/ehf2.14799. https://pubmed.ncbi.nlm.nih.gov/38656659/
9. 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/