Abstract:
:Ochratoxin A (OTA) is a toxin produced by fungi such as Aspergillus spp. and Penicillium spp. The key target organ of OTA toxicity is the kidney, and it is known that epithelial-to-mesenchymal transition (EMT) leading to fibrosis is enhanced after long-term exposure of the kidney to OTA. However, the mechanisms responsible for this onset are not precisely known. Therefore, the purpose of this study was to investigate the mechanism of OTA-induced EMT and fibrosis in human proximal tubule HK-2 cells and mouse kidneys. Cells were treated for 48 h with various concentrations of OTA (50, 100, and 200 nM) and mice underwent oral administration of various doses of OTA (200 and 1000 μg/kg body weight) for 12 weeks. Blood urea nitrogen and creatinine levels were increased in the serum of OTA-treated mice, and fibrosis was observed in kidney tissues. Furthermore, alpha-smooth muscle actin (α-SMA) and fibronectin levels were increased, and E-cadherin level was decreased by OTA in both HK-2 cells and kidney tissues. In addition, the expression levels of TGF-β, smad2/3, and β-catenin were increased after OTA treatment. α-SMA, E-cadherin, and fibronectin were shown to be regulated by the activation of transcription factors, smad2/3 and β-catenin. These results demonstrated that OTA induces EMT and renal fibrosis through Smad2/3 and β-catenin signaling pathways in vitro and in vivo.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Pyo MC,Chae SA,Yoo HJ,Lee KWdoi
10.1007/s00204-020-02829-9subject
Has Abstractpub_date
2020-09-01 00:00:00pages
3329-3342issue
9eissn
0340-5761issn
1432-0738pii
10.1007/s00204-020-02829-9journal_volume
94pub_type
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