Patulin Induces Acute Kidney Injury in Mice through Autophagy-Ferroptosis Pathway

Patulin (PAT) is a common mycotoxin, widely found in cereals, seafood, nuts, and especially in fruits and theirproducts. Exposure to this mycotoxin has been reported to induce kidney injury. However, the possible mechanism remains unclear.In our study, short-term high-dose intake of PAT caused acute kidney injury (AKI) in mice. We performed high-throughputtranscriptional sequencing to identify differentially expressed genes (DEGs) between the treatment and control groups. Theferroptosis signaling pathway had the highest enrichment, suggesting ferroptosis is involved in PAT-induced AKI. Further, theexistence of ferroptosis and autophagy was confirmed by observing the changes of mitochondria morphology and the formation ofautophagosomes by electron microscopy. And the expression of solute carrier family 7 member 11 (SLC7A11), glutathioneperoxidase 4 (GPX4), p62, nuclear receptor coactivator 4 (NCOA4), and ferritin heavy chain 1 (FTH1) were downregulated,whereas acyl-CoA synthase long-chain family member 4 (ACSL4), transferrin (TF), LC3, and ferritin light chain (FTL) expressionwere upregulated in PAT-exposed mice. These results suggested autophagy-dependent ferroptosis occurred in the animal model.This view has also been confirmed in the human renal tubular epithelial cell (HKC) experiments. Autophagy inhibitor 3-methyladenine (3MA) attenuated PAT-induced ferroptosis and the iron contents in HKC cells. Simultaneous autophagy-dependentferroptosis can be inhibited by ferroptosis inhibitors ferrostatin-1 (Fer-1) and desferrioxamine (DFO). In general, this study providesa new perspective for exploring the new mechanism of acute kidney injury caused by PAT

Automated summary

In this study, researchers found that autophagy-dependent ferroptosis plays a critical role in acute kidney injury induced by PAT. This view was also confirmed in human cell experiments.