Ochratoxin A induces glomerular injury through activating the ERK/NF-κB signaling pathway
Ochratoxin A induces glomerular injury through activating the ERK/NF-κB signaling pathway
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赭曲霉毒素 A 通过激活 ERK/NF-κ B 信号通路诱导肾小球损伤
DOI：
10.1016/j.fct.2020.111516
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发表时间：
2020-09-01
影响因子：
4.3
通讯作者：
Huang, Kehe
中科院分区：
文献类型：
--
作者：
Le, Guannan;Yuan, Xin;Huang, Kehe
据报道赭曲霉毒素A （OTA）可引起人类和动物近端肾小管肾毒性。然而，OTA对肾小球的毒性研究甚少。我们研究了ota诱导的肾小球损伤及其潜在机制。小鼠隔天腹腔注射OTA(0、0.5、1.5和2.5 mg/kg b.w.)，连续3周。OTA暴露降低了体重增加率、肾脏指数和血清肌酐和血尿素氮水平。它还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vimentin的表达。将人系膜细胞（HMC）用OTA （0-8 μ M）处理48 h， OTA对HMC细胞的抑制率升高，IL-6、tgf - β、α - sma和vimentin表达呈剂量依赖性上调。此外，它还增强了ERK1/2和p65的磷酸化，I κ pa b - α的降解和p65易位到细胞核。nf - κ B和ERK1/2抑制剂可减轻ota引起的毒性。总之，这些结果表明，OTA暴露通过激活ERK/NF-03信号通路诱导肾小球损伤，并为OTA诱导肾毒性的研究提供了新的见解。
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-alpha, IL-6, COX-2, TGF-beta, alpha-SMA and vimentin in a dose-dependent manner. Human mesangial cells (HMC) were treated with OTA (0-8 mu M) for 48 h. Treatment of HMC cells with OTA increased cell inhibition rate, up-regulated the expression of IL-6, TGF-beta, alpha-SMA and vimentin in a dose-dependent manner. Additionally, it enhanced the phosphorylation of ERK1/2 and p65, degradation of I kappa B-alpha and translocation of p65 into the nucleus. OTA-induced toxicity was attenuated by NF-kappa B and ERK1/2 inhibitors. In conclusion, these results suggest that OTA exposure induces glomerular injury via activation of the ERK/NF-03 signaling pathway, and provide novel insights into the research of OTA induced nephrotoxicity.