UV-B stimulation can induce retinopathy, whose pathogenesis is currently unclear. UV-B mediated inflammation in retinal endothelial cells is reported to be involved in the pathogenesis of retinopathy. S14G-humanin (HNG) is a neuroprotective peptide that has recently been reported to exert significant anti-inflammatory effects and protective properties against cell death. The present study aims to investigate the protective effects of HNG against UV-B-challenged retinal endothelial cells and explore the underlying mechanism. UV-B radiation was used to induce an injury model in human retinal endothelial cells (HRECs). First, exposure to UV-B induced the expression of TXNIP. Additionally, we found that treatment with HNG inhibited the activation of the TXNIP/NLRP3 signaling pathway and mitigated the excessive release of IL-1β and IL-18 in UV-B-challenged HRECs. UV-B increased the expression of the transcriptional factor endothelial growth response-1 (Egr-1). Interestingly, overexpression of Egr-1 increased the luciferase activity of the TXNIP promoter as well as the mRNA and protein expression of TXNIP. In contrast, the knockdown of Egr-1 reduced the expression of TXNIP under both the normal and UV-B exposure conditions. Importantly, treatment with HNG attenuated UV-B-induced expression of Egr-1. However, overexpression of Egr-1 abolished the inhibitory effects of HNG-induced activation of NLRP3 as well as the production of IL-1β and IL-18. Taken together, our findings reveal that HNG protected retinal endothelial cells from UV-B-induced NLRP3 inflammation activation through inhibiting TXNIP mediated by Egr-1.

UV-B 刺激可诱发视网膜病变，其发病机制目前尚不清楚。据报道，UV-B 介导的视网膜内皮细胞炎症与视网膜病变的发病机制有关。S14G-humanin (HNG) 是一种神经保护肽，最近据报道它具有显着的抗炎作用和防止细胞死亡的保护特性。本研究旨在研究 HNG 对 UV-B 挑战的视网膜内皮细胞的保护作用并探索其潜在机制。UV-B 辐射用于在人视网膜内皮细胞 (HRECs) 中诱导损伤模型。首先，暴露于 UV-B 会诱导 TXNIP 的表达。此外，我们发现用 HNG 治疗抑制了 TXNIP/NLRP3 信号通路的激活，并减轻了 UV-B 攻击的 HREC 中 IL-1β 和 IL-18 的过度释放。UV-B 增加了转录因子内皮生长反应-1 (Egr-1) 的表达。有趣的是，Egr-1 的过表达增加了 TXNIP 启动子的荧光素酶活性以及 TXNIP 的 mRNA 和蛋白质表达。相反，在正常和 UV-B 暴露条件下，Egr-1 的敲低降低了 TXNIP 的表达。重要的是，用 HNG 治疗减弱了 UV-B 诱导的 Egr-1 表达。然而，Egr-1 的过表达消除了 HNG 诱导的 NLRP3 激活以及 IL-1β 和 IL-18 产生的抑制作用。综合起来，