Ochratoxin A (OTA) was reported to induce proximal tubules nephrotoxicity in humans and animals. However, the toxicity of OTA on glomeruli has rarely been studied. We investigated OTA-induced glomerular injury and the underlying mechanisms. Mice were intraperitoneally treated with OTA (0, 0.5, 1.5 and 2.5 mg/kg b.w.) on alternate day for 3 weeks. OTA exposure decreased the weight gain ratio, the kidney index and increased the levels of serum creatinine and blood urea nitrogen. It induced also fragmentation and atrophy in glomeruli, and increased the expression of TNF-α, IL-6, COX-2, TGF-β, α-SMA and vimentin in a dose-dependent manner. Human mesangial cells (HMC) were treated with OTA (0–8 μM) for 48 h. Treatment of HMC cells with OTA increased cell inhibition rate, up-regulated the expression of IL-6, TGF-β, α-SMA and vimentin in a dose-dependent manner. Additionally, it enhanced the phosphorylation of ERK1/2 and p65, degradation of IκB-α and translocation of p65 into the nucleus. OTA-induced toxicity was attenuated by NF-κB and ERK1/2 inhibitors. In conclusion, these results suggest that OTA exposure induces glomerular injury via activation of the ERK/NF-κB signaling pathway, and provide novel insights into the research of OTA induced nephrotoxicity.

据报道曲霉毒素A（OTA）在人和动物中引起近端小管肾毒性。但是，很少研究过OTA对肾小球的毒性。我们调查了OTA引起的肾小球损伤及其潜在机制。每隔一天用OTA（0、0.5、1.5和2.5 mg / kg bw）腹膜内处理小鼠3周。暴露于OTA会降低体重增加率，肾脏指数并增加血清肌酐和血液尿素氮的水平。它也诱导肾小球碎裂和萎缩，并以剂量​​依赖性方式增加TNF-α，IL-6，COX-2，TGF-β，α-SMA和波形蛋白的表达。用OTA（0–8μM）处理人系膜细胞（HMC）48小时。OTA处理HMC细胞可提高细胞抑制率，上调IL-6，TGF-β，α-SMA和波形蛋白呈剂量依赖性。此外，它还增强了ERK1 / 2和p65的磷酸化，IκB-α的降解以及p65向核内的转运。OTA诱导的毒性被NF-κB和ERK1 / 2抑制剂减弱。总之，这些结果表明，OTA暴露通过激活ERK /NF-κB信号传导途径诱导肾小球损伤，并为OTA诱导的肾毒性研究提供了新的见识。