Patulin (PAT) is a mycotoxin produced by various fungal species that commonly contaminate apples and other fruit products. PAT is associated with glutathione (GSH) depletion and oxidative stress. Cytoprotective and antioxidant (AO) enzymes limit toxic outcomes and confer resistance to oxidative stress by influencing the expression of cytoprotective genes. The induction of these genes is tightly regulated by transcription factor nuclear factor erythroid 2 p45–related factor 2 (NRF2), a potential target of microRNA (miR)-144. 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 of NRF2, 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 of NRF2 (p = 0.0378) as well as the target genes CAT (p = 0.0273), NQO1 (p = 0.0156), HMOX (p = 0.0249), and GSTA1 (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.

展青霉素 (PAT) 是一种真菌毒素，由多种真菌产生，通常会污染苹果和其他水果产品。PAT 与谷胱甘肽 (GSH) 消耗和氧化应激有关。细胞保护和抗氧化 (AO) 酶通过影响细胞保护基因的表达来限制毒性结果并赋予对氧化应激的抵抗力。这些基因的诱导受到转录因子核因子类红细胞 2 p45 相关因子 2 (NRF2) 的严格调控，NRF2 是 microRNA (miR)-144 的潜在靶标。本研究旨在确定 miR-144 在人胚胎肾 (HEK293) 细胞中 PAT 暴露后 NRF2 通路激活中的可能作用。HEK293 细胞暴露于不同的 PAT 浓度（0、0.2、0.5、1 μmol/L；24 小时）。Keap1、NRF2、使用蛋白质印迹法对磷酸化 (p) NRF2 (ser40) 进行定量。基因表达NRF2、SOD2、CAT、GPx、NQO1、GSTA1、HMOX和 miR-144 通过 qPCR 进行评估。PAT 显着降低 miR-144 ( p  = 0.0249) 并同时增加 NRF2 蛋白表达、稳定性和激活，如 pNRF2 ( p  = 0.0216) 表达增加和总 NRF2 减少 ( p  = 0.0237) 所证明。这与 qPCR 数据一致，该数据显示NRF2 ( p  = 0.0378) 以及靶基因CAT ( p  = 0.0273)、NQO1 ( p = 0.0156)、HMOX ( p  = 0.0249) 和GSTA1 ( p  = 0.0237)。在 Keap1 表达中没有观察到变化 ( p  = 0.6444)。该研究表明 microRNA 在 PAT 诱导的毒性中具有机械作用。PAT 降低 miR-144 表达，导致 NRF2 通路激活和 AO 基因表达升高。