Ochratoxin a induces hepatic fibrosis through TGF ‐β receptor I/Smad2/3 signaling pathway
| Autor: | Seung A Chae, Min Cheol Pyo, Hee Joon Yoo, Kwang‐Won Lee |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Liver Cirrhosis
Epithelial-Mesenchymal Transition Health Toxicology and Mutagenesis Smad2 Protein General Medicine Management Monitoring Policy and Law Toxicology Fibrosis Ochratoxins Transforming Growth Factor beta1 Transforming Growth Factor beta Humans RNA Messenger Receptors Transforming Growth Factor beta Signal Transduction |
| Zdroj: | Environmental Toxicology. 37:2084-2095 |
| ISSN: | 1522-7278 1520-4081 |
| DOI: | 10.1002/tox.23552 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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