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

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.

• Authors: Fang Gan, Yajiao Zhou, Gang Qian, Da Huang, Lili Hou, Dandan Liu, Xingxiang Chen, Tian Wang, Ping Jiang, Xingen Lei, Kehe Huang
• Journal: Environmental pollution (Barking, Essex : 1987) (Environ Pollut) Vol. 238 Pg. 656-662 (Jul 2018) ISSN: 1873-6424 [Electronic] England
• PMID: 29614475 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Ochratoxins
• ochratoxin A

Topics

• Animals
• Autophagy (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Circoviridae Infections
• Circovirus
• Kidney (drug effects, metabolism)
• MAP Kinase Signaling System (drug effects)
• Ochratoxins (metabolism, toxicity)
• Phosphorylation
• Signal Transduction
• Swine (virology)