Abstract：
BACKGROUND: Retinal pigment epithelial (RPE) cells have a pivotal function in preserving the equilibrium of the retina and moderating the immunological interaction between the choroid and the retina. This study primarily focuses on delineating the protective effect offered by Kaempferol (Kae) against RPE cell damage.
METHODS: Bioinformatics analysis was performed on the GSE30719 dataset to identify hub genes associated with RPE. Subsequently, we analyzed the impact of Kae on RPE apoptosis, cell viability, and inflammatory response through cell experiments, and explored the interaction between hub genes and Kae.
RESULTS: Based on the GSE30719 dataset, nine hub genes (ISG15, IFIT1, IFIT3, STAT1, OASL, RSAD2, IRF7, MX2, and MX1) were identified, all of which were highly expressed in the GSE30719 case group. Kae could boost the proliferative activity of RPE cells caused by lipopolysaccharide (LPS), as well as reduce apoptosis and the generation of inflammatory factors (tumor necrosis factor receptor (TNFR), interleukin-1beta (IL-1β)) and cytokines (IL-1, IL-6, IL-12). STAT1 was shown to inhibit cell proliferation, promote apoptosis, and secrete IL-1/IL-6/IL-12 in LPS-induced RPE cells. Moreover, IRF7 was found to interact with STAT1 in LPS-induced RPE cells, and STAT1 could maintain IRF7 levels through deubiquitination. In addition, we also found that the protective effect of Kae on LPS-induced RPE cell injury was mediated through STAT1/IRF7 axis.
CONCLUSIONS: This study provided evidence that Kae protects RPE cells via regulating the STAT1/IRF7 signaling pathways, indicating its potential therapeutic relevance in the diagnosis and management of retinal disorders linked with RPE cell damage.
METHODS: Bioinformatics analysis was performed on the GSE30719 dataset to identify hub genes associated with RPE. Subsequently, we analyzed the impact of Kae on RPE apoptosis, cell viability, and inflammatory response through cell experiments, and explored the interaction between hub genes and Kae.
RESULTS: Based on the GSE30719 dataset, nine hub genes (ISG15, IFIT1, IFIT3, STAT1, OASL, RSAD2, IRF7, MX2, and MX1) were identified, all of which were highly expressed in the GSE30719 case group. Kae could boost the proliferative activity of RPE cells caused by lipopolysaccharide (LPS), as well as reduce apoptosis and the generation of inflammatory factors (tumor necrosis factor receptor (TNFR), interleukin-1beta (IL-1β)) and cytokines (IL-1, IL-6, IL-12). STAT1 was shown to inhibit cell proliferation, promote apoptosis, and secrete IL-1/IL-6/IL-12 in LPS-induced RPE cells. Moreover, IRF7 was found to interact with STAT1 in LPS-induced RPE cells, and STAT1 could maintain IRF7 levels through deubiquitination. In addition, we also found that the protective effect of Kae on LPS-induced RPE cell injury was mediated through STAT1/IRF7 axis.
CONCLUSIONS: This study provided evidence that Kae protects RPE cells via regulating the STAT1/IRF7 signaling pathways, indicating its potential therapeutic relevance in the diagnosis and management of retinal disorders linked with RPE cell damage.
摘要：
背景：视网膜色素上皮（RPE）细胞在保持视网膜平衡和调节脉络膜与视网膜之间的免疫相互作用方面具有关键作用。这项研究主要集中在描述山奈酚（Kae）对RPE细胞损伤的保护作用。
方法：对GSE30719数据集进行生物信息学分析，以鉴定与RPE相关的hub基因。随后，我们分析了Kae对RPE细胞凋亡的影响，细胞活力，通过细胞实验和炎症反应，并探索了hub基因与Kae之间的相互作用。
结果：基于GSE30719数据集，九个hub基因(ISG15、IFIT1、IFIT3、STAT1、OASL、RSAD2、IRF7、MX2和MX1)被鉴定，所有这些在GSE30719病例组中高表达。Kae可以促进脂多糖（LPS）引起的RPE细胞的增殖活性，以及减少细胞凋亡和炎症因子（肿瘤坏死因子受体（TNFR）的产生，白细胞介素-1β(IL-1β)和细胞因子(IL-1、IL-6、IL-12)。STAT1被证明可以抑制细胞增殖，促进细胞凋亡，并在LPS诱导的RPE细胞中分泌IL-1/IL-6/IL-12。此外，在LPS诱导的RPE细胞中发现IRF7与STAT1相互作用，STAT1可以通过去泛素化来维持IRF7水平。此外,我们还发现Kae对LPS诱导的RPE细胞损伤的保护作用是通过STAT1/IRF7轴介导的。
结论：本研究提供了Kae通过调节STAT1/IRF7信号通路保护RPE细胞的证据，表明其在与RPE细胞损伤相关的视网膜疾病的诊断和管理中的潜在治疗相关性。
方法：对GSE30719数据集进行生物信息学分析，以鉴定与RPE相关的hub基因。随后，我们分析了Kae对RPE细胞凋亡的影响，细胞活力，通过细胞实验和炎症反应，并探索了hub基因与Kae之间的相互作用。
结果：基于GSE30719数据集，九个hub基因(ISG15、IFIT1、IFIT3、STAT1、OASL、RSAD2、IRF7、MX2和MX1)被鉴定，所有这些在GSE30719病例组中高表达。Kae可以促进脂多糖（LPS）引起的RPE细胞的增殖活性，以及减少细胞凋亡和炎症因子（肿瘤坏死因子受体（TNFR）的产生，白细胞介素-1β(IL-1β)和细胞因子(IL-1、IL-6、IL-12)。STAT1被证明可以抑制细胞增殖，促进细胞凋亡，并在LPS诱导的RPE细胞中分泌IL-1/IL-6/IL-12。此外，在LPS诱导的RPE细胞中发现IRF7与STAT1相互作用，STAT1可以通过去泛素化来维持IRF7水平。此外,我们还发现Kae对LPS诱导的RPE细胞损伤的保护作用是通过STAT1/IRF7轴介导的。
结论：本研究提供了Kae通过调节STAT1/IRF7信号通路保护RPE细胞的证据，表明其在与RPE细胞损伤相关的视网膜疾病的诊断和管理中的潜在治疗相关性。
