ANXA1,也称为Annexin A1,是一种重要的钙结合蛋白,属于Annexin家族。Annexins是一类具有保守结构的蛋白质,能够与磷脂结合并调节细胞膜的流动性,参与多种生物学过程,如细胞信号传导、细胞增殖、分化、凋亡和炎症反应。ANXA1在多种细胞类型中表达,包括免疫细胞、内皮细胞、上皮细胞和神经元细胞。ANXA1具有多种生物学功能,包括抗炎、抗凋亡、调节细胞粘附和信号传导等。
ANXA1在多种疾病中发挥重要作用。例如,在原发性硬化性胆管炎(PSC)中,ANXA1的表达水平升高与疾病的高风险和T细胞浸润相关[1]。ANXA1的表达与PSC患者的不良预后相关,并且ANXA1可能通过影响免疫细胞浸润和纤维化等过程参与PSC的发病机制。此外,ANXA1的表达还与肾细胞癌(RCC)对酪氨酸激酶抑制剂(TKIs)的耐药性相关[2]。ANXA1在RCC细胞和患者组织中表达上调,并且ANXA1的稳定性与AKT通路的激活相关,从而促进RCC对TKIs的耐药性。此外,ANXA1还与动脉粥样硬化、糖尿病肾病、胶质瘤、三阴性乳腺癌(TNBC)和早期发作帕金森病(EOPD)等疾病的发生和发展相关[3,4,5,6,7,8,9,10]。
ANXA1在动脉粥样硬化中发挥抗炎作用,通过调节胆固醇转运和抗炎活性来保护血管。ANXA1与ABCA1相互作用,促进胆固醇的流出和细胞外ANXA1的释放,从而发挥抗炎作用[3]。在糖尿病肾病中,ANXA1通过调节脂质代谢来改善疾病进展。ANXA1的缺失会加重糖尿病肾病小鼠的肾损伤,包括蛋白尿、肾小球基质扩张和肾小管间质病变。ANXA1的缺失还会促进肾内脂质积累和线粒体改变[4]。在胶质瘤中,ANXA1的表达水平升高与不良预后相关,并且ANXA1是胶质瘤的独立预后因素。ANXA1可能通过影响细胞外基质(ECM)受体相互作用和粘着斑信号通路来发挥作用[5]。在TNBC中,ANXA1和ANXA2的表达水平升高与不良预后相关,并且ANXA1和ANXA2是TNBC的独立预后因素[6]。在EOPD中,ANXA1的突变可能与疾病的发病机制相关,但ANXA1突变在EOPD中的发生频率较低[7,8]。在胃癌中,CTHRC1的表达上调与肿瘤相关巨噬细胞浸润和肿瘤血管生成相关,并且CTHRC1的表达与ANXA1/FPR1通路相关[9]。
综上所述,ANXA1是一种重要的钙结合蛋白,参与多种生物学过程,并在多种疾病中发挥重要作用。ANXA1的研究有助于深入理解细胞信号传导、细胞粘附、炎症反应和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Zhang, Jian, Wang, Huiwen, Liu, Jinqing, Fu, Lei, Peng, Shifang. 2023. ANXA1 is identified as a key gene associated with high risk and T cell infiltration in primary sclerosing cholangitis. In Human genomics, 17, 86. doi:10.1186/s40246-023-00534-z. https://pubmed.ncbi.nlm.nih.gov/37735492/
2. Xiong, Wei, Zhang, Bin, Yu, Haixin, Yi, Lu, Jin, Xin. 2021. RRM2 Regulates Sensitivity to Sunitinib and PD-1 Blockade in Renal Cancer by Stabilizing ANXA1 and Activating the AKT Pathway. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 8, e2100881. doi:10.1002/advs.202100881. https://pubmed.ncbi.nlm.nih.gov/34319001/
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7. Gibbs, Lee D, Vishwanatha, Jamboor K. 2017. Prognostic impact of AnxA1 and AnxA2 gene expression in triple-negative breast cancer. In Oncotarget, 9, 2697-2704. doi:10.18632/oncotarget.23627. https://pubmed.ncbi.nlm.nih.gov/29416802/
8. Gagliardi, Monica, Procopio, Radha, Talarico, Mariagrazia, Quattrone, Aldo, Annesi, Grazia. 2023. ANXA1 mutation analysis in Italian patients with early onset PD. In Neurobiology of aging, 125, 123-124. doi:10.1016/j.neurobiolaging.2023.01.014. https://pubmed.ncbi.nlm.nih.gov/36828691/
9. Li, Chunyu, Ou, Ruwei, Gu, Xiaojing, Wu, Ying, Shang, Huifang. 2022. ANXA1 and the risk for early-onset Parkinson's disease. In Neurobiology of aging, 112, 212-214. doi:10.1016/j.neurobiolaging.2022.01.009. https://pubmed.ncbi.nlm.nih.gov/35240489/
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