PCV2 infection aggravates ochratoxin A-induced nephrotoxicity via autophagy involving p38 signaling pathway in vivo and in vitro

Fang Gan; Yajiao Zhou; Gang Qian; Da Huang; Lili Hou; Dandan Liu; Xingxiang Chen; Tian Wang; Ping Jiang; Xingen Lei; Kehe Huang

doi:10.1016/j.envpol.2018.03.032

PCV2 infection aggravates ochratoxin A-induced nephrotoxicity via autophagy involving p38 signaling pathway in vivo and in vitro

Environ Pollut. 2018 Jul:238:656-662. doi: 10.1016/j.envpol.2018.03.032. Epub 2018 Mar 31.

Authors

Fang Gan¹, Yajiao Zhou², Gang Qian², Da Huang², Lili Hou², Dandan Liu², Xingxiang Chen², Tian Wang³, Ping Jiang², Xingen Lei⁴, Kehe Huang⁵

Affiliations

¹ 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.
² 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.
³ College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China.
⁴ Department of Animal Science, Cornell University, Ithaca, NY, 14853, USA. Electronic address: XL20@cornell.edu.
⁵ 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. Electronic address: khhuang@njau.edu.cn.

PMID: 29614475
DOI: 10.1016/j.envpol.2018.03.032

Abstract

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.

Keywords: Autophagy; Nephrotoxicity; Ochratoxin A; Porcine circovirus type 2; p38 MAPK signaling pathway.

MeSH terms

Animals
Autophagy / drug effects
Cell Line
Cell Survival / drug effects
Circoviridae Infections
Circovirus
Kidney / drug effects*
Kidney / metabolism
MAP Kinase Signaling System / drug effects
Ochratoxins / metabolism
Ochratoxins / toxicity*
Phosphorylation
Signal Transduction
Swine / virology*

Substances

Ochratoxins
ochratoxin A