Gsdma,也称为Gasdermin A,是Gasdermin家族中的一员。Gasdermin家族是一组结构相关的蛋白质,包括GSDMA、GSDMB、GSDMC、GSDMD、GSDME/DNFA5和PVJK/GSDMF。GSDMs具有一个C端抑制域、一个细胞毒性N端域和一个灵活的连接域(除了GSDMF)。GSDM-NT域可以被切割并释放,形成膜上的大寡聚孔,从而促进细胞焦亡。GSDMs在多种生理和病理过程中发挥作用,包括细胞分化、凝血、炎症和肿瘤发生[2]。GSDMA在哺乳动物中的功能尚不完全清楚,但研究表明GSDMA在肿瘤免疫逃逸中发挥着重要作用。在胶质瘤中,高表达GSDMA的患者预后较差。GSDMA敲低可以增强CD8+ T细胞的浸润水平。此外,高GSDMA表达与胶质母细胞瘤患者的不良抗PD-L1治疗结果相关,提示GSDMA可能是胶质瘤患者免疫治疗的潜在生物标志物[1]。GSDMA还与系统性硬化症(SSc)的易感性相关。GSDMA和PRDM1是系统性硬化症的易感基因,它们与免疫功能相关,并与其他自身免疫性疾病相关[3]。此外,GSDMA与哮喘相关。哮喘相关多态性在17q12-21位点影响GSDMA在幼稚CD4+ T细胞中的甲基化和基因表达[4]。GSDMA还与炎症性肠病(IBD)的易感性相关。GSDMA、GSDMB和LRRC3C是炎症性肠病易感性的贡献者[5]。GSDMA在多种疾病中发挥重要作用,包括肿瘤免疫逃逸、系统性硬化症、哮喘和炎症性肠病。GSDMA的研究有助于深入理解GSDM家族的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. Zhang, Ruicheng, Song, Qiuya, Lin, Xiaoqian, Geng, Deqin, Gao, Dianshuai. 2023. GSDMA at the crossroads between pyroptosis and tumor immune evasion in glioma. In Biochemical and biophysical research communications, 686, 149181. doi:10.1016/j.bbrc.2023.149181. https://pubmed.ncbi.nlm.nih.gov/37924669/
2. Zou, Ju, Zheng, Yixiang, Huang, Yan, Kang, Rui, Chen, Ruochan. 2021. The Versatile Gasdermin Family: Their Function and Roles in Diseases. In Frontiers in immunology, 12, 751533. doi:10.3389/fimmu.2021.751533. https://pubmed.ncbi.nlm.nih.gov/34858408/
3. Terao, Chikashi, Kawaguchi, Takahisa, Dieude, Philippe, Matsuda, Fumihiko, Allanore, Yannick. 2017. Transethnic meta-analysis identifies GSDMA and PRDM1 as susceptibility genes to systemic sclerosis. In Annals of the rheumatic diseases, 76, 1150-1158. doi:10.1136/annrheumdis-2016-210645. https://pubmed.ncbi.nlm.nih.gov/28314753/
4. Madore, Anne-Marie, Pain, Lucile, Boucher-Lafleur, Anne-Marie, Pastinen, Tomi, Laprise, Catherine. 2020. Asthma-associated polymorphisms in 17q12-21 locus modulate methylation and gene expression of GSDMA in naïve CD4+ T cells. In Journal of genetics and genomics = Yi chuan xue bao, 47, 171-174. doi:10.1016/j.jgg.2020.03.002. https://pubmed.ncbi.nlm.nih.gov/32312674/
5. Söderman, Jan, Berglind, Linda, Almer, Sven. 2015. Gene Expression-Genotype Analysis Implicates GSDMA, GSDMB, and LRRC3C as Contributors to Inflammatory Bowel Disease Susceptibility. In BioMed research international, 2015, 834805. doi:10.1155/2015/834805. https://pubmed.ncbi.nlm.nih.gov/26484354/