Downregulation of Acat1 by miR-21 may participate in liver fibrosis upon chronic DDT exposure.

Mikhail D Chanyshev, Andrey A Yarushkin, Elena V Koldysheva, Elena L Lushnikova, Lyudmila F Gulyaeva

Toxicology mechanisms and methods 2020 Oct

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The main objective of the present study was to investigate the toxic effect of long-term exposure to DDT (2,2-dichlorodiphenyl-1,1,1-trichloroethane) on rat livers. Female Wistar rats were treated with once-weekly i.p. doses of DDT (10 and 50 mg/kg) for 12 weeks. Histological analysis revealed significant changes in the liver structure, especially at a dose of 50 mg/kg, which consistent with a fibrotic state. Long-term DDT exposure increased micro RNA-21 (miR-21) level and decreased Acetyl-CoA acetyltransferase 1 (Acat1) mRNA and protein levels in a dose-dependent manner. A dual-luciferase reporter assay confirmed the regulation of the rat Acat1 3'-UTR by miR-21. Previous studies have described the involvement of ACAT1 in fibrogenesis; thus, regulation of the Acat1 gene by miR-21 may play a role in DDT exposure-mediated liver fibrosis.

Citation

Mikhail D Chanyshev, Andrey A Yarushkin, Elena V Koldysheva, Elena L Lushnikova, Lyudmila F Gulyaeva. Downregulation of Acat1 by miR-21 may participate in liver fibrosis upon chronic DDT exposure. Toxicology mechanisms and methods. 2020 Oct;30(8):562-569