Transcriptomic characterization of bovine primary cultured hepatocytes; a cross-comparison with a bovine liver and the Madin-Darby bovine kidney cells

Bovine primary cultured hepatocytes (CHs) are widely used in vitro models for liver toxicity testing. However, little is known about their whole-transcriptome profile and its resemblance to the normal liver tissue. In the present study, we profiled – by microarray - the whole-transcriptome of bovine CHs (n =4) and compared it with the transcriptomic landscape of control liver samples (n =8), as well the Madin-Darby bovine kidney (MDBK) cells (n =4). Compared with liver tissue, the bovine CHs relatively expressed (fold change> 2, P < 0.05) about 2155 and 2073 transcripts at a lower and higher abundance, respectively. Of those expressed at a lower abundance, many were drug biotransformation enzyme-coding genes, such as the cytochrome P450 family (CYPs), sulfotransferases, methyltransferases, and glutathione S-transferases. Also, several drug transporters and solute carriers were expressed at a lower abundance in bovine CHs. ‘Drug metabolism’, ‘PPAR signaling’, and ‘metabolism of xenobiotics by CYPs’ were among the most negatively-enriched pathways in bovine CHs compared with liver. A qPCR cross-validation using 8 selected genes evidenced a high correlation (r =0.95, P=0.001) with the corresponding microarray results. Although from a kidney origin, and albeit to a lower extent compared to bovine CHs, the MDBK cells showed a basal expression of many CYP-coding genes. Our study provides a whole-transcriptome-based evidence for the bovine CHs and hepatic tissue resemblance. Overall, the bovine CHs' transcriptomic profile might render it unreliable as an in vitro model to study drug metabolism.