Yuan Jie, Gao Chongyong, Xin Wang, Meng Fanlin, Zhang Hong
Department of Geriatrics, Chengdu Qingbaijiang District Traditional Chinese Medicine Hospital, Chengdu, China.
Emergency Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
PLoS One. 2025 Jun 6;20(6):e0324586. doi: 10.1371/journal.pone.0324586. eCollection 2025.
Ulcerative colitis (UC) is a recurrent inflammatory condition of the bowel with a multifaceted pathogenesis, including programmed cell death, oxidative stress, and immune-mediated inflammation. As a recently identified type of cell death, disulfidptosis has an unclear role in UC.
We analyzed clusters of disulfidptosis-related genes (DRGs) and immune cell infiltration in 361 patients with UC from the GSE73661and GSE92415 datasets. Differentially expressed genes (DEGs) were identified using unsupervised clustering methods, and hub genes were selected using machine learning algorithms. Additionally, potential key components of potential traditional Chinese medicines for the treatment of UC were predicted based on hub genes. Finally, experimental validation was performed through qRT-PCR, western blotting, and immunohistochemistry.
We identified two molecular clusters related to disulfidptosis, each showing significant heterogeneity in gene expression and immune profiles. Hub genes associated with disulfidptosis, CXCL1, HMGCS2, AQP8, and SLC26A2, were further screened and validated. Additionally, potential traditional Chinese medicines for UC were predicted. 3'-Methoxydaidzein (MHD), a key constituent of Puerariae Radix, inhibited LPS-induced inflammatory responses in Caco2 cells and alleviated DSS-induced colonic injury in UC mice via upregulation of SLC26A2.
DRGs demonstrate strong discriminatory power in distinguishing UC subtypes. Cluster with high expression of SLC26A2 showed a UC phenotype with a milder degree of damage. Additionally, we identified the hub gene SLC26A2 as playing a significant role in UC, and MHD demonstrates potential as a targeted therapeutic strategy for UC.
溃疡性结肠炎（UC）是一种肠道复发性炎症性疾病，其发病机制具有多方面性，包括程序性细胞死亡、氧化应激和免疫介导的炎症。作为最近发现的一种细胞死亡类型，二硫化物诱导的细胞死亡在UC中的作用尚不清楚。
我们分析了来自GSE73661和GSE92415数据集的361例UC患者中二硫化物诱导的细胞死亡相关基因（DRGs）簇和免疫细胞浸润情况。使用无监督聚类方法鉴定差异表达基因（DEGs），并使用机器学习算法选择枢纽基因。此外，基于枢纽基因预测了治疗UC的潜在中药的潜在关键成分。最后，通过qRT-PCR、蛋白质免疫印迹和免疫组织化学进行实验验证。
我们鉴定出两个与二硫化物诱导的细胞死亡相关的分子簇，每个簇在基因表达和免疫谱方面均表现出显著的异质性。进一步筛选并验证了与二硫化物诱导的细胞死亡相关的枢纽基因CXCL1、HMGCS2、AQP8和SLC26A2。此外，还预测了治疗UC的潜在中药。葛根的关键成分3'-甲氧基大豆苷元（MHD）通过上调SLC26A2抑制LPS诱导的Caco2细胞炎症反应，并减轻DSS诱导的UC小鼠结肠损伤。
DRGs在区分UC亚型方面具有很强的鉴别能力。SLC26A2高表达的簇显示出损伤程度较轻的UC表型。此外，我们确定枢纽基因SLC26A2在UC中起重要作用，并且MHD显示出作为UC靶向治疗策略的潜力。
