2. Academic Validation
  3. Fumonisin B1 induces nephrotoxicity via autophagy mediated by mTORC1 instead of mTORC2 in human renal tubule epithelial cells

Fumonisin B1 induces nephrotoxicity via autophagy mediated by mTORC1 instead of mTORC2 in human renal tubule epithelial cells

  • Food Chem Toxicol. 2021 Mar;149:112037. doi: 10.1016/j.fct.2021.112037.
Lili Hou 1,  Xin Yuan 1,  Guannan Le 1,  Ziman Lin 1,  Fang Gan 1,  Haolei Li 1,  Kehe Huang 2
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China; Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China.
  • 2 College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China; Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China. Electronic address: khhuang@njau.edu.cn.
PMID: 33548371 DOI: 10.1016/j.fct.2021.112037
Abstract

Fumonisin B1 (FB1), a worldwide contaminating mycotoxin, can cause global food issue. It has been reported that FB1 is related to chronic kidney disease of unknown etiology. However, the study of FB1-induced nephrotoxicity in vitro is very limited and the mechanism is unknown. Human renal tubule epithelial (HK-2) cells were used in this study. The results showed that FB1 exposure could decrease cell viability, induce cell Apoptosis and up-regulate the expression of Kim-1, collagen I, α-SMA and TGF-β1. In addition, Autophagy was activated after FB1 exposure, including the conversion of LC3 and up-regulation of ATGs. Furthermore, Autophagy Inhibitor 3-MA could block FB1-induced abnormalities. And antioxidant Enzymes (Gpx1 and Gpx4) were obviously down-regulated and intracellular ROS levels displayed an ascent trend as FB1 exposure concentrations increased. Employing of antioxidant NAC could suppress FB1-induced nephrotoxicity and Autophagy. FB1 inhibited the phosphorylation of p70 S6k, a downstream protein of mTORC1. Also, oxidative stress, Autophagy and phosphorylation of p70 S6k induced by FB1 was inhibited by MHY1485, an activator of mTOR. But the phosphorylation of Akt, a downstream protein of mTORC2 showed no change with or without MHY1485. Taken together, FB1 induced nephrotoxicity via Autophagy mediated by mTORC1 instead of mTORC2 in HK-2 cells.

Keywords

Autophagy; Fumonisin B1; HK-2 cells; Nephrotoxicity; Oxidative stress; mTORC1.

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