TY - JOUR
T1 - Downregulation of Acat1 by miR-21 may participate in liver fibrosis upon chronic DDT exposure
AU - Chanyshev, Mikhail D.
AU - Yarushkin, Andrey A.
AU - Koldysheva, Elena V.
AU - Lushnikova, Elena L.
AU - Gulyaeva, Lyudmila F.
PY - 2020/10/12
Y1 - 2020/10/12
N2 - 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.
AB - 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.
KW - Acat1
KW - DDT
KW - liver fibrosis
KW - mir-21
KW - rat
KW - TARGET
KW - GENE
KW - MICRORNAS
KW - EXPRESSION
KW - PESTICIDES
KW - ACAT1
UR - http://www.scopus.com/inward/record.url?scp=85087515047&partnerID=8YFLogxK
U2 - 10.1080/15376516.2020.1777493
DO - 10.1080/15376516.2020.1777493
M3 - Article
C2 - 32508177
AN - SCOPUS:85087515047
VL - 30
SP - 562
EP - 569
JO - Toxicology Mechanisms and Methods
JF - Toxicology Mechanisms and Methods
SN - 1537-6516
IS - 8
ER -