Emerging Alternaria Toxins Drive LX-2 Cells Transdifferentiation into Myofibroblasts for Liver Fibrosis and CotA Detoxification
- J Agric Food Chem. 2026 Apr 29;74(16):13162-13178. doi: 10.1021/acs.jafc.5c15968.
- 1. Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
- 2. Institute of Quality Standards & Testing Technology for Agro-Products, Xinjiang Uygur Autonomous Region Academy of Agricultural Sciences/Key Laboratory of Agro-Products Qualityand Safety of Xinjiang/Laboratory of Quality and Safety Risk Assessment for AgroProducts (Urumqi), Ministry of Agriculture and Rural Affairs/Key Laboratory of Functional Nutrition and Health of Characteristic Agricultural Products in Desert Oasis Ecological Region (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Urumqi 830091, China.
- 3. NHC Key Laboratory of Food Safety Risk Assessment, Chinese Academy of Medical Sciences Research Unit (No. 2019RU014), China National Center for Food Safety Risk Assessment, Beijing 100022, China.
Alternariol (AOH), alternariol monomethyl ether (AME), and tenuazonic acid (TeA) are three major emerging Alternaria toxins in food. In this lncRNA-mRNA omics-based study, we first decrypt the blueprint: how emerging Alternaria toxins induce hepatic stellate cell LX-2 transdifferentiation for liver fibrosis. AOH and AME caused the fibrotic marker α-smooth muscle actin, extracellular matrix Collagen expression, and cell contraction, while TeA had no significant effect. Mechanistically, AOH, AME, and AAT (their combination) activated the NF-κB pathway and induced Ferroptosis and AMPK/Akt/m-TOR-related Autophagy. Meanwhile, lncRNAs associated with hepatotoxicity were analyzed, and core LncRNAs associated with transdifferentiation were identified. Furthermore, we also proposed a CotA degradation strategy to eliminate the AOH hepatotoxicity. In summary, the present study identifies the potential hepatotoxicity of Alternaria toxins, introduces a CotA laccase-mediated detoxification approach, and lays a foundation for subsequent research and control strategies targeting hepatotoxicity.