Angptl2,也称为Angiopoietin-like protein 2,是一种在多种细胞和组织中表达的蛋白质,参与血管生成、造血和肿瘤发生等多种生物学过程。Angptl2基因的表达受多种因素的调控,包括DNA甲基化、转录因子和microRNA等。Angptl2蛋白的生物学功能与其受体有关,包括整合素α5β1和白细胞免疫球蛋白样受体B2(LILRB2)等。
Angptl2在多种疾病中发挥重要作用。在结直肠癌中,Angptl2在肿瘤微环境中高表达,并且与肿瘤的转移和患者的预后密切相关[1]。Angptl2通过促进肿瘤相关成纤维细胞(CAFs)和巨噬细胞的浸润,加速了结直肠癌的转移[1]。在高血压中,Angptl2的表达在高血压大鼠中升高,并且与血管平滑肌细胞(VSMCs)的增殖、迁移和侵袭有关[2]。Angptl2的基因敲低可以抑制Ang II诱导的VSMCs的增殖、迁移和侵袭[2]。在急性冠状动脉综合征(ACS)患者中,Angptl2基因的启动子区域甲基化水平降低,这可能与炎症环境有关[3]。Angptl2的基因敲低可以抑制LPS诱导的巨噬细胞的焦亡,并增加自噬水平,从而减轻急性肺损伤[5]。在女性冠心病患者中,Angptl2基因的启动子区域甲基化水平降低,这可能与冠心病的发生发展有关[6]。Angptl2可以促进软骨细胞的炎症反应,通过整合素α5β1和MAPKs信号通路发挥作用[7]。在甲状腺癌中,Angptl2的表达水平升高,并且与肿瘤的增殖、迁移和侵袭密切相关[4]。Angptl2还可以通过促进β-catenin信号通路来促进肠道肿瘤的发生[8]。Angptl2还可以促进白血病的发展,通过血管内皮细胞释放的含有Angptl2的小细胞外囊泡发挥作用[9]。
综上所述,Angptl2是一种重要的蛋白质,参与多种生物学过程,包括血管生成、造血和肿瘤发生等。Angptl2在多种疾病中发挥重要作用,包括结直肠癌、高血压、冠心病、急性肺损伤、甲状腺癌和白血病等。Angptl2的基因敲低可以抑制多种细胞的功能,包括VSMCs的增殖、迁移和侵袭,巨噬细胞的焦亡,以及肿瘤细胞的增殖、迁移和侵袭等。Angptl2的研究有助于深入理解其生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Liu, Xiangxiang, Qin, Jian, Nie, Junjie, Wang, Shukui, Pan, Yuqin. 2023. ANGPTL2+cancer-associated fibroblasts and SPP1+macrophages are metastasis accelerators of colorectal cancer. In Frontiers in immunology, 14, 1185208. doi:10.3389/fimmu.2023.1185208. https://pubmed.ncbi.nlm.nih.gov/37691929/
2. Yang, Haiying, Liu, Jie, Chen, Xue, Li, Guobin. 2021. Angptl2 gene knockdown is critical for abolishing angiotensin II-induced vascular smooth muscle cell proliferation and migration. In Biochemistry and cell biology = Biochimie et biologie cellulaire, 100, 59-67. doi:10.1139/bcb-2021-0191. https://pubmed.ncbi.nlm.nih.gov/34860608/
3. Nguyen, Albert, Mamarbachi, Maya, Turcot, Valérie, Nigam, Anil, Thorin, Eric. 2016. Lower Methylation of the ANGPTL2 Gene in Leukocytes from Post-Acute Coronary Syndrome Patients. In PloS one, 11, e0153920. doi:10.1371/journal.pone.0153920. https://pubmed.ncbi.nlm.nih.gov/27101308/
4. Yang, Longyan, Sun, Rongxin, Wang, Yan, Ji, Zhili, Zhao, Dong. 2019. Expression of ANGPTL2 and its impact on papillary thyroid cancer. In Cancer cell international, 19, 204. doi:10.1186/s12935-019-0908-9. https://pubmed.ncbi.nlm.nih.gov/31384179/
5. Yang, Fan, Chen, Muhu, Liu, Ying, Yu, Youwei, Deng, Lu. . ANGPTL2 knockdown induces autophagy to relieve alveolar macrophage pyroptosis by reducing LILRB2-mediated inhibition of TREM2. In Journal of cellular and molecular medicine, 28, e18280. doi:10.1111/jcmm.18280. https://pubmed.ncbi.nlm.nih.gov/38758159/
6. Zhou, Jianqing, Chen, Li, Yang, Xi, Peng, Ping, Lian, Jiangfang. 2018. Preliminary study of the relationship between promoter methylation of the ANGPTL2 gene and coronary heart disease. In Journal of clinical laboratory analysis, 33, e22702. doi:10.1002/jcla.22702. https://pubmed.ncbi.nlm.nih.gov/30461060/
7. Takano, Mami, Hirose, Naoto, Sumi, Chikako, Asakawa, Yuki, Tanimoto, Kotaro. 2019. ANGPTL2 Promotes Inflammation via Integrin α5β1 in Chondrocytes. In Cartilage, 13, 885S-897S. doi:10.1177/1947603519878242. https://pubmed.ncbi.nlm.nih.gov/31581797/
8. Horiguchi, Haruki, Kadomatsu, Tsuyoshi, Yumoto, Shinsei, Moroishi, Toshiro, Oike, Yuichi. 2022. Tumor cell-derived ANGPTL2 promotes β-catenin-driven intestinal tumorigenesis. In Oncogene, 41, 4028-4041. doi:10.1038/s41388-022-02405-8. https://pubmed.ncbi.nlm.nih.gov/35831580/
9. Huang, Dan, Sun, Guohuan, Hao, Xiaoxin, Zheng, Junke, Cheng, Tao. . ANGPTL2-containing small extracellular vesicles from vascular endothelial cells accelerate leukemia progression. In The Journal of clinical investigation, 131, . doi:10.1172/JCI138986. https://pubmed.ncbi.nlm.nih.gov/33108353/