title: Both canonical and noncanonical Wnt signalling may be required for detoxification following ETP class mycotoxin exposure.
abstract: Fungal infections (mycotoxicoses) are a growing global threat for both health and food production, and the available tools for effective detection, monitoring and treatment remain limited. Mycotoxins of the so-called ETP class can cause disease in humans (notably immunocompromised clinical patients) and otherwise healthy ruminant production animals. Understanding the molecular responses caused by ETP toxicity responses will inform diagnostics and guide possible interventions. Here we provide empirical evidence that exposure of hepatic cells to the ETP mycotoxin Sporidesmin A may trigger both canonical and noncanonical Wnt signalling, mediated through miRNA regulation, and regulate the particular expression of CYP2C family members. These data suggest cellular adaptation to mycotoxin exposure is an epigenetically dependent process leading to the co-ordination of multiple Wnt pathways to drive appropriate downstream detoxification mechanisms.
authors.affiliation: College of Animal Science and Technology, Nanjing Agriculture University, 210095, PR China; Liggins Institute, University of Auckland, 1023, New Zealand. Electronic address: zhangjinbi@njau.edu.cn.
authors.forename: Jinbi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology, Nanjing Agriculture University, 210095, PR China. Electronic address: owwa@njau.ecu.cn.
authors.forename: Zengxiang
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Liggins Institute, University of Auckland, 1023, New Zealand. Electronic address: a.sheppard@auckland.ac.nz.
authors.forename: Allan
authors.initials: A
authors.lastname: Sheppard
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D019295:Computational Biology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D008658:Inactivation, Metabolic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013173:Sporidesmins / Q000145:classification / Q000378:metabolism / Q000633:toxicity*; D013997:Time Factors; D014162:Transfection; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D013173:Sporidesmins; C400322:cytochrome P-450 CYP2C subfamily; D003577:Cytochrome P-450 Enzyme System; C001873:sporidesmin
keywords: CYP450; Detoxification; Mycotoxin; Sporidesmin A; Wnt signalling; miRNA