PCV2 infection aggravates ochratoxin A-induced nephrotoxicity via autophagy involving p38 signaling pathway in vivo and in vitro
PCV2 infection aggravates ochratoxin A-induced nephrotoxicity via autophagy involving p38 signaling pathway in vivo and in vitro
复制标题
在体内和体外，PCV2感染通过涉及p38信号通路的自噬加重赭曲霉毒素A诱导的肾毒性。
DOI：
10.1016/j.envpol.2018.03.032
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发表时间：
2018-07-01
影响因子：
8.9
通讯作者：
Huang, Kehe
中科院分区：
文献类型：
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作者：
Gan, Fang;Zhou, Yajiao;Huang, Kehe
据报道，赭曲霉毒素 A (OTA) 可引起动物和人类的肾毒性。猪圆环病毒2型（PCV2）可诱发猪皮炎和肾病综合征。迄今为止，人们对病毒感染是否会加重霉菌毒素引起的毒性知之甚少。本工作旨在研究PCV2感染对OTA所致肾毒性的影响及其体内外机制。体内结果表明，猪肾脏中Atg5、LC3 II和p62蛋白的表达表明，PCV2感染加剧了OTA诱导的生长性能差、肾毒性、p38磷酸化和自噬。体外结果表明，PCV2 感染显着加重 OTA 诱导的肾毒性（细胞活力、膜联蛋白 V/PI 结合和 caspase 3 活性），并诱导 PK15 细胞中的 p38 磷酸化和自噬。 p38抑制剂降低了PCV2感染和OTA联合治疗诱导的Atg5和LC3蛋白表达。添加自噬抑制剂3-MA或CQ减轻了PCV2感染对OTA诱导的肾毒性的加重作用。 Atg5 特异性 siRNA 消除了 PCV2 感染对 OTA 诱导的肾毒性的加重作用。综上所述，这些数据表明体内和体外 PCV2 感染通过 p38 介导的自噬加重了 OTA 诱导的肾毒性。 (C) 2018 Elsevier Ltd. 保留所有权利。
Ochratoxin A (OTA) is reported to induce nephrotoxicity in animals and humans. Porcine circovirus type 2 (PCV2) could induce porcine dermatitis and nephropathy syndrome. To date, little is known whether virus infection aggravates mycotoxin-induced toxicity. This work aimed to study the effects of PCV2 infection on OTA-induced nephrotoxicity and its mechanism in vivo and vitro. The results in vivo showed that PCV2 infection aggravated OTA-induced poor growth performance, nephrotoxicity, p38 phosphorylation and autophagy as demonstrated by Atg5, LC3 II and p62 protein expressions in kidney of pigs. The results in vitro indicated that PCV2 infection significantly aggravated OTA-induced nephrotoxicity as demonstrated by cell viabilities, annexin V/PI binding and caspase 3 activities, and induced p38 phosphorylation and autophagy in PK15 cells. p38 inhibitor decreased Atg5 and LC3 protein expression induced by PCV2 infection and OTA combined treatment. Adding autophagy inhibitor 3-MA or CQ alleviated the aggravating effects of PCV2 infection on OTA-induced nephrotoxicity. Atg5-specific siRNA eliminated the aggravating effects of PCV2 infection on OTA-induced nephrotoxicity. Taken together, these data indicate that in vivo and in vitro PCV2 infection aggravated OTA-induced nephrotoxicity via p38-mediated autophagy. (C) 2018 Elsevier Ltd. All rights reserved.