S100A9,也称为钙结合蛋白A9,是一种属于S100蛋白家族的钙结合蛋白。S100蛋白家族是一类小分子钙结合蛋白,在细胞内发挥多种生物学功能,包括细胞分化、增殖、凋亡、炎症反应和细胞信号传导等。S100A9主要在髓系细胞中表达,包括巨噬细胞和单核细胞,在炎症反应和免疫应答中发挥重要作用[1]。
S100A9与许多疾病的发生和发展密切相关。例如,在乳腺癌中,BRCA1基因突变导致S100A9-CXCL12信号通路激活,促进肿瘤进展和免疫抑制微环境的形成,使肿瘤对免疫治疗产生耐药性[2]。在银屑病和银屑性关节炎中,S100A9表达增加,导致中性粒细胞浸润和炎症反应加重,而S100A9的缺失则导致疾病严重程度加剧[3]。此外,S100A9在败血症引起的急性肺损伤中也发挥重要作用,其通过IL-17-NFκB-caspase-3信号通路加剧肺损伤和上皮细胞凋亡[4]。S100A9还与败血症引起的急性肺损伤中的巨噬细胞M1极化有关,通过抑制TLR4/MyD88/NFκB信号通路和NLRP3细胞焦亡通路来减轻炎症和细胞凋亡[5]。此外,S100A9在心肌梗死后的抑郁样行为中也发挥作用,通过调节巨噬细胞和微胶质细胞的炎症反应来改善心脏功能和抑郁样行为[6]。S100A9还与炎症性肠病和心力衰竭的免疫相关基因标记和免疫浸润特征有关[7]。此外,S100A9的表达受到C/EBPδ转录因子的调控,C/EBPδ通过JMJD3介导的H3K27me3去甲基化来控制S100a8和S100a9基因的动态转录[8]。S100A9还与非酒精性脂肪肝和多囊卵巢综合征的发生和发展有关[9]。此外,S100A9在儿童败血症休克中也发挥重要作用,与免疫细胞浸润有关[10]。
综上所述,S100A9是一种重要的钙结合蛋白,在多种疾病中发挥重要作用,包括乳腺癌、银屑病、急性肺损伤、心肌梗死、炎症性肠病和心力衰竭等。S100A9通过多种信号通路和免疫细胞调节炎症反应和免疫应答,影响疾病的发生和发展。因此,S100A9的研究有助于深入理解炎症反应和免疫应答的机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Li, Jianjie, Shu, Xiaodong, Xu, Jun, Deng, Chuxia, Xu, Xiaoling. 2022. S100A9-CXCL12 activation in BRCA1-mutant breast cancer promotes an immunosuppressive microenvironment associated with resistance to immunotherapy. In Nature communications, 13, 1481. doi:10.1038/s41467-022-29151-5. https://pubmed.ncbi.nlm.nih.gov/35304461/
2. Mellor, Liliana F, Gago-Lopez, Nuria, Bakiri, Latifa, Schett, Georg, Wagner, Erwin F. 2022. Keratinocyte-derived S100A9 modulates neutrophil infiltration and affects psoriasis-like skin and joint disease. In Annals of the rheumatic diseases, 81, 1400-1408. doi:10.1136/annrheumdis-2022-222229. https://pubmed.ncbi.nlm.nih.gov/35788494/
3. Pei, Hui, Chen, Jianming, Qu, Jie, Lu, Zhongqiu. 2024. S100A9 exacerbates sepsis-induced acute lung injury via the IL17-NFκB-caspase-3 signaling pathway. In Biochemical and biophysical research communications, 710, 149832. doi:10.1016/j.bbrc.2024.149832. https://pubmed.ncbi.nlm.nih.gov/38588614/
4. Gong, Chen, Ma, Ji, Deng, Ya, Shen, Shichun, Ding, Shenggang. 2024. S100A9-/- alleviates LPS-induced acute lung injury by regulating M1 macrophage polarization and inhibiting pyroptosis via the TLR4/MyD88/NFκB signaling axis. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 172, 116233. doi:10.1016/j.biopha.2024.116233. https://pubmed.ncbi.nlm.nih.gov/38308971/
5. Sun, Yize, Wang, Zheyi, Hou, Jiqiu, Wang, Chao, Zhao, Haibin. 2022. Shuangxinfang Prevents S100A9-Induced Macrophage/Microglial Inflammation to Improve Cardiac Function and Depression-Like Behavior in Rats After Acute Myocardial Infarction. In Frontiers in pharmacology, 13, 832590. doi:10.3389/fphar.2022.832590. https://pubmed.ncbi.nlm.nih.gov/35814253/
6. Luo, Xu, Wang, Rui, Zhang, Xin, Deng, Siwei, Xie, Wen. 2023. Identification CCL2,CXCR2,S100A9 of the immune-related gene markers and immune infiltration characteristics of inflammatory bowel disease and heart failure via bioinformatics analysis and machine learning. In Frontiers in cardiovascular medicine, 10, 1268675. doi:10.3389/fcvm.2023.1268675. https://pubmed.ncbi.nlm.nih.gov/38034382/
7. Jauch-Speer, Saskia-Larissa, Herrera-Rivero, Marisol, Ludwig, Nadine, Roth, Johannes, Fehler, Olesja. 2022. C/EBPδ-induced epigenetic changes control the dynamic gene transcription of S100a8 and S100a9. In eLife, 11, . doi:10.7554/eLife.75594. https://pubmed.ncbi.nlm.nih.gov/35543413/
8. Chen, Yong, Ma, Leikai, Ge, Zhouling, Pan, Yizhao, Xie, Lubin. 2022. Key Genes Associated With Non-Alcoholic Fatty Liver Disease and Polycystic Ovary Syndrome. In Frontiers in molecular biosciences, 9, 888194. doi:10.3389/fmolb.2022.888194. https://pubmed.ncbi.nlm.nih.gov/35693550/
9. Fan, Jiajie, Shi, Shanshan, Qiu, Yunxiang, Liu, Mingnan, Shu, Qiang. 2022. Analysis of signature genes and association with immune cells infiltration in pediatric septic shock. In Frontiers in immunology, 13, 1056750. doi:10.3389/fimmu.2022.1056750. https://pubmed.ncbi.nlm.nih.gov/36439140/
10. Talley, Sarah, Valiauga, Rasa, Anderson, Lillian, Choudhry, Mashkoor A, Campbell, Edward M. 2021. DSS-induced inflammation in the colon drives a proinflammatory signature in the brain that is ameliorated by prophylactic treatment with the S100A9 inhibitor paquinimod. In Journal of neuroinflammation, 18, 263. doi:10.1186/s12974-021-02317-6. https://pubmed.ncbi.nlm.nih.gov/34758843/