College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China; Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China; College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China.
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China; Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China.
Environ Pollut. 2018 Jul;238:656-662. doi: 10.1016/j.envpol.2018.03.032. Epub 2018 Mar 31.
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.
赭曲霉毒素 A（OTA）被报道在动物和人类中具有肾毒性。猪圆环病毒 2 型（PCV2）可引起猪皮炎肾病综合征。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。本研究旨在研究 PCV2 感染对 OTA 诱导的肾毒性的影响及其在体内和体外的机制。体内研究结果表明，PCV2 感染加重了 OTA 诱导的猪生长性能下降、肾毒性、p38 磷酸化和自噬，表现为肾组织中 Atg5、LC3 II 和 p62 蛋白表达增加。体外研究结果表明，PCV2 感染显著加重了 OTA 诱导的 PK15 细胞毒性、Annexin V/PI 结合和 caspase 3 活性增加，以及 p38 磷酸化和自噬。p38 抑制剂降低了 PCV2 感染和 OTA 联合处理诱导的 Atg5 和 LC3 蛋白表达。添加自噬抑制剂 3-MA 或 CQ 可减轻 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。
