Ustiloxins induce kidney injury via the TLR2/MAPK/NF-κB pathway

Ustiloxins levels are associated with abnormal renal function indicators, suggesting that ustiloxins may be risk factors for kidney damage. Given limited evidence on the underlying mechanisms, this study investigated the mechanisms linking the TLR2/MAPK/NF-κB pathway to ustiloxin-induced kidney damage via transcriptomic and in vivo experiments. Male mice were gavaged with ustiloxins at doses of 2, 5, and 12.5 mg/kg daily for three months. Transcriptomic data indicated that ustiloxins may mediate kidney damage via the TLR2/MAPK/NF-κB pathway. Analysis of indicators related to renal function revealed that exposure to ustiloxins resulted in impaired kidney function, with varying degrees of elevation in the levels of blood urea nitrogen (BUN), creatinine (CR), and uric acid (UA). H&E staining revealed pathological damage in kidney sections after ustiloxin exposure. Compared with the control group, Masson's staining showed increased fibrosis in the renal interstitium of the ustiloxin-exposed group. Western blot analysis indicated that toxin exposure significantly increased the protein expression of p-p65, p-p38, p-ERK, and p-JNK in the kidneys of the mice. qRT‒PCR and Western blot analyses also exhibited that the mRNA and protein expression levels of transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA), and vimentin were significantly increased in the ustiloxin-exposed group compared with those in the control group. Thus, the present data indicated that exposure to ustiloxins may result in kidney damage via the TLR2/MAPK/NF-κB pathway.