T-2 toxin inhibits osteoblastic differentiation and mineralization involving mutual regulation between Wnt signaling pathway and autophagy

Zhang, Jian; Wang, Peiyan; Song, Miao; Zhang, Xuliang; Huo, Siming; Du, Jiayu; Li, Bo; Cao, Zheng; Li, Yanfei

doi:10.1016/j.cbi.2022.110266

Cited by 1 publication

(1 citation statement)

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“…34 Its main pathological feature is liver injury, 35 which will eventually develop into cirrhosis and hepatocellular carcinoma if left untreated. 36 T-2 toxin, the most toxic of class A trichosporene mycotoxins, 37 is an unavoidable environmental crop and feed contaminant. 38 The results of a global survey (2008−2017) showed that the T-2 toxin detection rate in feed samples was about 19%, with a maximum concentration of 3051 μg/kg; 39 T-2 toxin was also detected in drinking water and Chinese medicine samples.…”

Section: ■ Discussionmentioning

confidence: 99%

Inhibition of Macrophage Pyroptosis─A New Therapeutic Strategy to Alleviate T-2 Toxin-Induced Subacute Liver Injury by Directly Competing with the Key Target

Xu,

Wu,

Zhao

et al. 2024

J. Agric. Food Chem.

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Multiple compounds are related to the development of liver injury, such as toxins, drugs, and environmental pollutants. Although there are reports that the T-2 toxin can cause liver injury, its toxic mechanism remains unclear, which further impedes the development of effective antidotes. In this study, CRISPR-Cas9 genome-wide screening technology was used to identify transformation-related protein 53 inducible nuclear protein 1 (trp53inp1) as a toxic target of the T-2 toxin. Mechanism studies have shown that the T-2 toxin induced pyroptosis of macrophages (J774A.1 cells) by activating the trp53inp1/NF-κB/NLRP3/GSDMD-N pathway, leading to a subacute liver injury. Also, the new drug berberine (BER) identified through virtual screening significantly alleviated the subacute liver injury by competitively binding trp53inp1 via His224; the effect was better than those of the positive control drugs N-acetylcysteine (NAC) and disulfiram (DSF). In summary, the above results indicate that trp53inp1 is a key target for T-2 toxin to induce subacute liver injury and that inhibiting macrophage pyroptosis is a new method for treating liver injury. In addition, this study provides a new method and strategy for the discovery of key disease targets and the search for effective drugs.

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