The Plk2 is a cellular stress-responsive factor that is induced in response to oxidative stress. However, the roles of Plk2 in acute kidney injury (AKI) have not been clarified. We previously found that Plk2 is an interacting factor of Nrf2 in response to cellular stress, since Plk2 is upregulated in the Nrf2-dependent network. Here, we show that the levels of p53, Plk2, p21^cip1, and chromatin-bound Nrf2 were all upregulated in kidney tissues of mice or NRK52E cells treated with either cisplatin or methotrexate. Upregulation of Plk2 by p53 led to an increase of Nrf2 in both soluble and chromatin fractions in cisplatin-treated NRK52E cells. Consistently, depletion of Plk2 suppressed the levels of Nrf2. Of note, Plk2 directly phosphorylated Nrf2 at Ser40, which facilitated its interaction with p21^cip1 and translocation into the nuclei for the activation of anti-oxidative and anti-inflammatory factors in response to AKI. Together, these findings suggest that Plk2 may serve as an anti-oxidative and anti-inflammatory regulator through the phosphorylation and activation of Nrf2 to protect kidney cells from kidney toxicants and that Plk2 and Nrf2 therefore work cooperatively for the protection and survival of kidney cells from harmful stresses.

Plk2 是一种细胞应激反应因子，是针对氧化应激而诱导的。然而，Plk2 在急性肾损伤 (AKI) 中的作用尚未明确。我们之前发现 Plk2 是 Nrf2 响应细胞应激的相互作用因子，因为 Plk2 在 Nrf2 依赖网络中上调。在这里，我们发现用顺铂或甲氨蝶呤处理的小鼠肾组织或 NRK52E 细胞中p53、Plk2、p21 ^{cip1和染色质结合 Nrf2 的水平均上调。}p53 对 Plk2 的上调导致顺铂处理的 NRK52E 细胞中可溶性部分和染色质部分中的 Nrf2 增加。一致地，Plk2 的消耗抑制了 Nrf2 的水平。值得注意的是，Plk2 直接在 Ser40 位点磷酸化 Nrf2，从而促进其与 p21 ^{cip1 的}相互作用并易位到细胞核中，从而激活 AKI 反应中的抗氧化和抗炎因子。总之，这些发现表明 Plk2 可能通过 Nrf2 的磷酸化和激活作为抗氧化和抗炎调节剂，保护肾细胞免受肾毒物的侵害，因此 Plk2 和 Nrf2 协同作用，保护肾细胞免受肾毒物的侵害并使其存活。有害的压力。