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

doi:10.1002/tox.23552

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 journal › Article › peer-review

12 Citations (Scopus)

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 language	English
Pages (from-to)	2084-2095
Number of pages	12
Journal	Environmental Toxicology
Volume	37
Issue number	8
DOIs	https://doi.org/10.1002/tox.23552
Publication status	Published - 2022 Aug

Bibliographical note

Funding Information:
This research was supported by the International Joint R&D Program, Agency for Korean National Food Cluster (Q1624241), Korea University Grant (K1910641), and School of Life Sciences & Biotechnology of Korea University for BK21PLUS. The authors thank the Institute of Biomedical Science & Food Safety, CJ‐Korea University Food Safety Hall (Seoul, South Korea) for providing the equipment and facilities.

Publisher Copyright:
© 2022 Wiley Periodicals LLC.

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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10.1002/tox.23552

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

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.",

keywords = "Ochratoxin A, Smad2, Smad3, TGF-β receptor I, liver fibrosis",

author = "Chae, {Seung A.} and Pyo, {Min Cheol} and Yoo, {Hee Joon} and Lee, {Kwang Won}",

note = "Funding Information: This research was supported by the International Joint R&D Program, Agency for Korean National Food Cluster (Q1624241), Korea University Grant (K1910641), and School of Life Sciences & Biotechnology of Korea University for BK21PLUS. The authors thank the Institute of Biomedical Science & Food Safety, CJ‐Korea University Food Safety Hall (Seoul, South Korea) for providing the equipment and facilities. Publisher Copyright: {\textcopyright} 2022 Wiley Periodicals LLC.",

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AU - Yoo, Hee Joon

AU - Lee, Kwang Won

N1 - Funding Information: This research was supported by the International Joint R&D Program, Agency for Korean National Food Cluster (Q1624241), Korea University Grant (K1910641), and School of Life Sciences & Biotechnology of Korea University for BK21PLUS. The authors thank the Institute of Biomedical Science & Food Safety, CJ‐Korea University Food Safety Hall (Seoul, South Korea) for providing the equipment and facilities. Publisher Copyright: © 2022 Wiley Periodicals LLC.

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N2 - 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.

AB - 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.

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

Abstract

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Keywords

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