Journal
TOXICOLOGY LETTERS
Volume 291, Issue -, Pages 149-157Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2018.04.014
Keywords
Ochratoxin A; Citrinin; Proximal tubule; Epithelial-to-mesenchymal transition; Tubulo-interstitial nephropathy
Categories
Funding
- Deutsche Forschungsgemeinschaft [SCHW1515/2-1, HU 730/12-1]
Ask authors/readers for more resources
Increased ochratoxin A (OTA) or citrinin (CIT) concentrations in food correlate with increased prevalence of tubule-interstitial nephropathy. We tested the hypothesis that co-exposure of human proximal tubule-derived epithelial cells (HK-2) to OTA and CIT promotes synergistic events indicative for inflammation, epithelial-to-mesenchymal-transition (EMT) or fibrosis. We measured markers of inflammation, EMT and fibrosis and investigated the role of MAP-kinases. Only concurrent but not individual exposure to OTA and CIT at nanomolar concentrations led to (i) an increase of TNF protein and mRNA, (ii) a decrease of COX-2 protein and mRNA, (iii) a decrease of E-cadherin protein and (iv) an increase of vimentin and alpha-SMA protein. Cell shape shifted from a cobblestone-to a spindle-like phenotype indicating EMT. Extra-and intracellular collagen III protein content was increased. Concomitant mRNA expression changes were observed for TNF, COX-2, E-cadherin and alpha-SMA indicating transcriptional regulation. This was not the case for vimentin and collagen III mRNA indicating posttranscriptional regulation. Inhibition of ERK 1/2 and JNK 1/2 reduced the effect on TNF but not on alpha-SMA mRNA indicating an involvement of these kinases. Phosphorylation of ERK1/2 was increased by CIT, OTA alone and the mycotoxin combination. In contrast, the phosphorylation of JNK1/2 was unchanged. In conclusion, nanomolar OTA and CIT act synergistically favouring nephropathic processes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available