Wang Yinghui, Wang Qimeng, Wang Mingming, Wang Xueling, Liu Qingzhen, Lv Shasha, Nie Huibin, Liu Gang
Department of Nephrology, Multidisciplinary Innovation Center for Nephrology The Second Hospital of Shandong University Jinan Shandong China.
Nephrology Research Institute of Shandong University Jinan Shandong China.
Food Sci Nutr. 2024 Nov 26;12(12):10800-10815. doi: 10.1002/fsn3.4617. eCollection 2024 Dec.
Recent research indicates that the activation of the NLRP3 inflammasome is crucial in the development of diabetic kidney disease (DKD). Epigallocatechin-3-gallate (EGCG), the predominant catechin in green tea, has been noted for its anti-inflammatory properties in DKD. However, the specific mechanisms are not yet fully understood. In this study, our objective was to explore the effects of EGCG on podocytes and in diabetic kidney disease (DKD) mice and investigate how EGCG modulates the TXNIP/NLRP3/IL-1β signaling pathway in DKD, both in podocytes and animal models. In vitro, we co-cultured podocytes with EGCG and detected the viability, apoptosis, inflammation and the TXNIP/NLRP3/IL-1β signaling pathway. In vivo, DKD mice were given EGCG via oral gavage, followed by evaluations of renal function, inflammation, and the aforementioned signaling pathway. Our findings revealed that oxidative stress, inflammatory cytokines, and the TXNIP/NLRP3/IL-1β pathway were upregulated in podocytes exposed to high glucose (HG) and in the kidneys of DKD mice. However, EGCG treatment reduced the expression of the NLRP3 inflammasome and its associated proteins, including TXNIP, ASC, caspase-1, and IL-1β, as well as the levels of ROS and inflammatory factors such as TNF-α, IL-6, and IL-18. Furthermore, in vivo, EGCG improved kidney function, reduced albuminuria and body weight, and alleviated renal pathological damage. In summary, our study suggests that EGCG mitigates inflammation in podocytes and DKD through the TXNIP/NLRP3/IL-1β signaling pathway, indicating potential benefits of EGCG or green tea in managing DKD.
最近的研究表明,NLRP3炎性小体的激活在糖尿病肾病(DKD)的发展中至关重要。表没食子儿茶素-3-没食子酸酯(EGCG)是绿茶中的主要儿茶素,其在DKD中的抗炎特性已为人所知。然而,具体机制尚未完全明确。在本研究中,我们的目的是探讨EGCG对足细胞以及糖尿病肾病(DKD)小鼠的影响,并研究EGCG如何在足细胞和动物模型中调节DKD中的TXNIP/NLRP3/IL-1β信号通路。在体外,我们将足细胞与EGCG共培养,并检测其活力、凋亡、炎症以及TXNIP/NLRP3/IL-1β信号通路。在体内,通过灌胃给予DKD小鼠EGCG,随后评估其肾功能、炎症以及上述信号通路。我们的研究结果显示,在暴露于高糖(HG)的足细胞以及DKD小鼠的肾脏中,氧化应激、炎性细胞因子和TXNIP/NLRP3/IL-1β通路均上调。然而,EGCG处理降低了NLRP3炎性小体及其相关蛋白的表达,包括TXNIP、ASC、半胱天冬酶-1和IL-1β,以及活性氧(ROS)水平和炎性因子如TNF-α、IL-6和IL-18的水平。此外,在体内,EGCG改善了肾功能,降低了蛋白尿和体重,并减轻了肾脏病理损伤。总之,我们的研究表明,EGCG通过TXNIP/NLRP3/IL-1β信号通路减轻足细胞和DKD中的炎症,这表明EGCG或绿茶在管理DKD方面具有潜在益处。