Cadmium (Cd) is a ubiquitous environmental pollutant of increasing worldwide concern to both humans and animals. Selenium yeast (Se-Y) is an organic selenium source that has been shown an advantage in antagonizing Cd-induced liver necroptosis in chicken. Herein, we described the discovery path of Se-Y antagonism in Cd-induced renal necroptosis in chicken through targeting miR-26a-5p/PTEN/PI3K/AKT signaling pathway. We set up four groups of chickens at random: control group (0.5 mg/kg Na₂SeO₃), Se-Y group (0.5 mg/kg Se-Y), Se-Y+Cd group (0.5 mg/kg Se-Y and 150 mg/kg CdCl₂) and Cd group (150 mg/kg CdCl₂ and 0.5 mg/kg Na₂SeO₃). Interestingly, we found Se-Y, but not Na₂SeO₃, significantly blocked Cd accumulation in the kidney and alleviated Cd-induced necroptosis through inhibiting the expression of RIP1, RIP3 and MLKL. Se-Y, activated miR-26a-5p expression, thereby down-regulated the expression of PTEN, resulting in the up-regulation of PI3K/AKT signaling pathway and the inhibition of oxidative stress in both Se-Y and Cd treated chickens. Besides that, Se-Y could also specifically reduce the expression levels of heat shock protein 60 (HSP60), HSP70 and HSP90 in Se-Y and Cd co-treated chickens. Taken together, our results showed that Se-Y has an added value to antagonize Cd-induced necroptosis in chicken kidney by regulating the miR-26a-5p/PTEN/PI3K/AKT signaling pathway and HSPs, indicating that Se-Y could serve as an effective antagonist on Cd-induced renal necroptosis in chickens.

镉 (Cd) 是一种无处不在的环境污染物，在全球范围内越来越受到人类和动物的关注。硒酵母 (Se-Y) 是一种有机硒源，已显示其在对抗 Cd 诱导的鸡肝坏死方面具有优势。在此，我们通过靶向 miR-26a-5p/PTEN/PI3K/AKT 信号通路描述了 Se-Y 拮抗作用在 Cd 诱导的鸡肾坏死中的发现途径。我们随机设置了四组鸡：对照组（0.5 mg/kg Na ₂ SeO ₃）、Se-Y组（0.5 mg/kg Se-Y）、Se-Y+Cd组（0.5 mg/kg Se- Y 和 150 mg/kg CdCl ₂）和 Cd 组（150 mg/kg CdCl ₂和 0.5 mg/kg Na ₂ SeO ₃）。有趣的是，我们发现了 Se-Y，但没有发现 Na ₂硒₃，通过抑制 RIP1、RIP3 和 MLKL 的表达，显着阻断了肾脏中 Cd 的积累并减轻了 Cd 诱导的坏死性凋亡。Se-Y 激活 miR-26a-5p 表达，从而下调 PTEN 的表达，导致 PI3K/AKT 信号通路上调，抑制 Se-Y 和 Cd 处理的鸡的氧化应激。除此之外，Se-Y还可以特异性降低Se-Y和Cd共处理鸡中热休克蛋白60（HSP60）、HSP70和HSP90的表达水平。综上所述，我们的结果表明，Se-Y 通过调节 miR-26a-5p/PTEN/PI3K/AKT 信号通路和 HSPs 具有拮抗 Cd 诱导的鸡肾坏死性凋亡的附加价值，表明 Se-Y 可以作为一种对 Cd 诱导的鸡肾坏死的有效拮抗剂。