MicroRNA profiling in kidney in pigs fed ochratoxin A contaminated diet.

ABSTRACT

OTA is a toxic metabolite produced by fungus belonging to Aspergillus and Penicillium genera. Kidney is the main target of this toxin; OTA is considered as one of the etiological factors at the origin of the human Balkan endemic nephropathy. microRNA are short non-coding transcrips (18-22 nucleotides in length) regulating key cellular processes. Various miRNAs have been established to play important roles in development of renal carcinoma and urothelial cancer. The objective of this study is to analyse the miRNA profiling in the kidney of piglets experimentally intoxicated with feed contaminated with OTA. Fifteen piglets (five pigs/group) were randomly distributed into 3 groups, fed normal diet (Group 1 control), or diets contaminated with OTA in two concentrations 50 µg OTA/kg feed (Group 2 50 µg OTA/kg feed) or 200 µg OTA/kg feed (Group 3 200 µg OTA/kg feed) for 28 days. At the end of the experiment blood samples were taken for serological analyses. Animals from control group and 200 µg OTA/kg feed were sacrificed and kidney samples were taken for histological and molecular analyses. As resulted from molecular profiling study there are 8 miRNA differentially expressed in OTA kidney vs control kidney, in which five miRNA were overexpressed in the kidney of OTA intoxicated animals miR-497 (FC = 6.34), miR-133a-3p (FC = 5.75), miR-423-3p (FC = 5.48), miR-34a (FC = 1.68), miR-542-3p (1.65) while three miRNA were downregulated miR-421-3p (FC = -3.96); miR-490 (FC = -3.87); miR-9840-3p (FC = -2.13). The altered miRNAs as effect of OTA are strongly connected to the engine of cancer, disturbing nodal points in different pathways, as TP53 signalling. This proof-of-concept study proves the actual utility of miRNAs as biomarkers of mycotoxin exposure, including OTA.