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黄曲霉毒素 A 上调 miR-155-5p 通过 TGF-β 调控的信号通路诱导肠道纤维化和上皮间质转化:体内外研究。

MiR-155-5p Elevated by Ochratoxin A Induces Intestinal Fibrosis and Epithelial-to-Mesenchymal Transition through TGF-β Regulated Signaling Pathway In Vitro and In Vivo.

机构信息

Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.

出版信息

Toxins (Basel). 2023 Jul 22;15(7):473. doi: 10.3390/toxins15070473.

Abstract

Ochratoxin A (OTA) is a mycotoxin that induces fibrosis and epithelial-to-mesenchymal transitions (EMT) in kidneys and livers. It enters our bodies through food consumption, where it is absorbed in the intestines. However, the impact of OTA on the intestines is yet to be studied. MicroRNA (miRNAs) are small non-coding single-stranded RNAs that block the transcription of specific mRNAs and are, therefore, involved in many biochemical processes. Our findings indicate that OTA can induce EMT and intestinal fibrosis both in vivo and in vitro. This study examines the impact of OTA on intestinal toxicity and the role of miRNAs in this process. Following OTA treatment, miR-155-5p was the most elevated miRNA by next-generation sequencing. Our research showed that OTA increased miR-155-5p levels through transforming growth factor β (TGF-β), leading to the development of intestinal fibrosis and EMT. Additionally, the study identified that the modulation of TGF-β and miR-155-5p by OTA is linked to the inhibition of CCAAT/enhancer-binding protein β (C/EBPβ) and Smad2/3 accumulation in the progression of intestinal fibrosis.

摘要

赭曲霉毒素 A(OTA)是一种真菌毒素,可诱导肾脏和肝脏纤维化和上皮-间充质转化(EMT)。它通过食物摄入进入人体,在肠道中被吸收。然而,OTA 对肠道的影响尚未得到研究。microRNA(miRNA)是一种小的非编码单链 RNA,可阻止特定 mRNA 的转录,因此参与许多生化过程。我们的研究结果表明,OTA 可在体内和体外诱导 EMT 和肠道纤维化。本研究探讨了 OTA 对肠道毒性的影响以及 miRNA 在这一过程中的作用。在 OTA 处理后,下一代测序显示 miR-155-5p 是上调最明显的 miRNA。我们的研究表明,OTA 通过转化生长因子-β(TGF-β)增加 miR-155-5p 的水平,导致肠道纤维化和 EMT 的发生。此外,研究还发现,OTA 对 TGF-β和 miR-155-5p 的调节与 CCAAT/增强子结合蛋白 β(C/EBPβ)和 Smad2/3 积累的抑制有关,这是肠道纤维化进展的关键。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e42/10467050/4ad05dde9273/toxins-15-00473-g001.jpg

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