Ochratoxin a induces hepatic fibrosis through TGF-β receptor I/Smad2/3 signaling pathway

Seung A. Chae, Min Cheol Pyo, Hee Joon Yoo, Kwang Won Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Ochratoxin A (OTA) is a mycotoxin generated by Penicillium and Aspergillus species. It is often found in cereals. We hypothesized that OTA exposure induces epithelial–mesenchymal transition (EMT), leading to liver fibrosis. In this research, we explored whether the TGF-β receptor I (TGF-β RI)/Smad2/3 signaling pathway is related to EMT-induced hepatic fibrosis. In vitro and in vivo experiments, mRNA and protein expression of liver fibrosis-related markers such as fibronectin, α-smooth muscle actin (α-SMA) and E-cadherin were assessed. The levels of alkaline phosphatase, alanine transaminase, aspartate aminotransferase, and total bilirubin, which are used to assess damage, increased. We also confirmed the increase in mRNA and protein expression of TGF-β RI, Smad2, and Smad3. The expression of liver fibrosis-related markers was decreased by siRNA-mediated silencing of Smad2/3, as well as TGF-RI suppression. Liver cells exposed to OTA showed enhanced TGF-β RI expression on the cell membrane. These results demonstrated that OTA induces hepatic fibrosis through TGF-β RI and Smad2/3 pathways in vitro and in vivo.

Original languageEnglish
Pages (from-to)2084-2095
Number of pages12
JournalEnvironmental Toxicology
Volume37
Issue number8
DOIs
Publication statusPublished - 2022 Aug

Keywords

  • Ochratoxin A
  • Smad2
  • Smad3
  • TGF-β receptor I
  • liver fibrosis

ASJC Scopus subject areas

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis

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