Patulin activates the NRF2 pathway by modulation of miR-144 expression in HEK293 cells

This study aims to determine a possible role for miR-144 in NRF2 pathway activation following PAT exposure in human embryonic kidney (HEK293) cells. HEK293 cells were exposed to varying PAT concentrations (0, 0.2, 0.5, 1 μmol/L ; 24 h). Protein expression of Keap1, NRF2, and phosphorylated (p) NRF2 (ser40) was quantified using western blotting. Gene expression ofNRF2,SOD2,CAT,GPx,NQO1,GSTA1,HMOX, and miR-144 were evaluated by qPCR. PAT significantly decreased miR-144 (p = 0.0249) and concomitantly increased NRF2 protein expression, stability, and activation as evidenced by increased pNRF2 (p = 0.0216) expression and decreased total NRF2 (p = 0.0237). This was consistent with qPCR data which showed increased transcript levels ofNRF2 (p = 0.0378) as well as the target genesCAT (p = 0.0273),NQO1 (p = 0.0156),HMOX (p = 0.0249), andGSTA1 (p = 0.0237). No changes were observed in Keap1 expression (p = 0.6444). This study implicates microRNAs in a mechanistic role in PAT-induced toxicity. PAT decreased miR-144 expression leading to NRF2 pathway activation and elevated AO gene expression.
Source: Mycotoxin Research - Category: Toxicology Source Type: research