Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, People's Republic of China.
Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, People's Republic of China.
Appl Microbiol Biotechnol. 2022 Apr;106(7):2637-2649. doi: 10.1007/s00253-022-11876-4. Epub 2022 Mar 16.
Oxalate-induced crystalline kidney injury is one of the most common types of crystalline nephropathy. Unfortunately, there is no effective treatment to reduce the deposition of calcium oxalate crystals and alleviate kidney damage. Thus, proactive therapeutic is urgently needed to alleviate the suffering it causes to patient. Here, we investigated whether IL-22 exerted nephroprotective effects to sodium oxalate-mediated kidney damage and its potential mechanism. Crystalline kidney injury models were developed in vitro and in vivo that was often observed in clinic. We provided evidence that IL-22 could effectively decrease the accumulation of ROS and mitochondrial damage in cell and animal models and reduce the death of TECs. Moreover, IL-22 decreased the expression of the NLRP3 inflammasome and mature IL-1β in renal tissue induced by sodium oxalate. Further studies confirmed that IL-22 could play an anti-inflammatory role by reducing the levels of cytokines such as IL-1β, IL-18, and TNF-α in serum. In conclusion, our study confirmed that IL-22 has protective effects on sodium oxalate-induced crystalline kidney injury by reducing the production of ROS, protecting mitochondrial membrane potential, and inhibiting the inflammatory response. Therefore, IL-22 may play a potential preventive role in sodium oxalate-induced acute renal injury. KEY POINTS: • IL-22 could reduce sodium oxalate-mediated cytotoxicity and ameliorate renal injury. • IL-22 could alleviate oxidative stress and mitochondrial dysfunction induced by sodium oxalate. • IL-22 could inhibit inflammatory response of renal injury caused by sodium oxalate.
草酸盐诱导的结晶性肾病损伤是最常见的结晶性肾病类型之一。不幸的是,目前尚无有效治疗方法来减少草酸钙晶体的沉积并减轻肾损伤。因此,迫切需要积极的治疗方法来减轻其给患者带来的痛苦。在这里,我们研究了 IL-22 是否对草酸钠介导的肾损伤发挥了肾脏保护作用及其潜在机制。在体外和体内建立了经常在临床上观察到的结晶性肾病损伤模型。我们提供的证据表明,IL-22 可以有效地减少细胞和动物模型中 ROS 的积累和线粒体损伤,减少 TEC 的死亡。此外,IL-22 降低了肾组织中由草酸钠诱导的 NLRP3 炎性小体和成熟的 IL-1β 的表达。进一步的研究证实,IL-22 通过降低血清中细胞因子(如 IL-1β、IL-18 和 TNF-α)的水平发挥抗炎作用。总之,我们的研究证实,IL-22 通过减少 ROS 的产生、保护线粒体膜电位和抑制炎症反应,对草酸钠诱导的结晶性肾病损伤具有保护作用。因此,IL-22 可能在草酸钠诱导的急性肾损伤中发挥潜在的预防作用。关键点:
IL-22 可以减轻草酸钠介导的细胞毒性并改善肾损伤。
IL-22 可以减轻草酸钠引起的氧化应激和线粒体功能障碍。
IL-22 可以抑制草酸钠引起的肾损伤的炎症反应。