Transcriptome Analysis Reveals the AhR, Smad2/3, and HIF-1 alpha Pathways as the Mechanism of Ochratoxin A Toxicity in Kidney Cells
- Authors
- Pyo, Min Cheol; Choi, In-Geol; Lee, Kwang-Won
- Issue Date
- 3월-2021
- Publisher
- MDPI
- Keywords
- ochratoxin A; aryl hydrocarbon receptor; Smad2; 3; hypoxia-inducible factor-1& #945; RNA-sequencing
- Citation
- TOXINS, v.13, no.3
- Indexed
- SCIE
SCOPUS
- Journal Title
- TOXINS
- Volume
- 13
- Number
- 3
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/128449
- DOI
- 10.3390/toxins13030190
- ISSN
- 2072-6651
- Abstract
- Ochratoxin A (OTA) is a mycotoxin occurring in foods consumed by humans. Recently, there has been growing global concern regarding OTA toxicity. The main target organ of OTA is the kidney, but the mechanism underlying renal toxicity is not well known. In this study, human-derived proximal tubular epithelial cells, HK-2 cells, were used for RNA-sequencing (RNA-seq) and transcriptome analysis. In total, 3193 differentially expressed genes were identified upon treatment with 200 nM OTA in HK-2 cells; of these, 2224 were upregulated and 969 were downregulated. Transcriptome analysis revealed that OTA significantly affects hypoxia, epithelial-mesenchymal transition (EMT), apoptosis, and xenobiotic metabolism pathways in kidney cells. Quantitative real-time PCR analysis showed gene expression patterns similar to RNA-seq analysis. Expression of EMT markers (E-cadherin and fibronectin), apoptosis markers (caspase-3 and Bax), and kidney injury molecule-1 (KIM-1) was suppressed by inhibiting AhR expression using siRNA, and the related transcription factors, Smad2/3, and HIF-1 alpha were downregulated. Smad2/3 suppression with siRNA could inhibit fibronetcin, caspase-3, Bax, and KIM-1 expression. Fibronetcin, caspase-3, Bax, and KIM-1 expression could be increased with HIF-1 alpha suppression with siRNA. Taken together, these findings suggest that OTA-mediated kidney toxicity via the AhR-Smad2/3-HIF-1 alpha signaling pathways leads to induction of EMT, apoptosis, and kidney injury.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - Graduate School > Department of Biotechnology > 1. Journal Articles
- College of Life Sciences and Biotechnology > Division of Food Bioscience and Technology > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.