Ochratoxin A-induced renal cortex fibrosis and epithelial-to-mesenchymal transition: molecular mechanisms of ochratoxin A-injury and potential effects of red wine.

Molecular Medicine
Nicoletta GaglianoMagda Gioia

Abstract

We characterized the effect of chronic ochratoxin A (OTA) on rat kidney cortex, analyzing collagen content and collagen turnover and the major markers of epithelial-to-mesenchymal transition (EMT), such as alpha-smooth muscle actin (alphaSMA), cadherins, and MMP-9. Because OTA nephrotoxicity is mediated by free radicals, we also investigated whether antioxidants in red wine provided protection for the kidney and attenuated OTA-induced EMT. Collagen content, determined by computerized analysis of Sirius red-stained kidney sections, increased in OTA, OTA-wine, and OTA-EtOH treated rats. In kidney cortex homogenates, COL-I and COL-III mRNA levels tended to rise in OTA treated rats, but were similar to CT after OTA-wine and OTA-EtOH administration. TIMP-1 gene expression was up-regulated in OTA, OTA-wine, and OTA-EtOH treated rats. LH2b mRNA/COL-I mRNA was significantly up-regulated in OTA-wine and OTA-EtOH treated rats, compared with CT and OTA alone. TGF-beta1 signaling tended to dominate after OTA, OTA-wine, and OTA-EtOH. MMP-1 protein levels were not affected. OTA induced proMMP-9 and alphaSMA overexpression, decreases of E-cadherin and N-cadherin, and DSC-2 up-regulation. OTA-wine caused a further, unexpected decrease of E- an...Continue Reading

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Citations

Dec 20, 2013·Toxins·Zheng HanAlfons Callebaut
Aug 18, 2020·Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment·Luana SchmidtPaula Rossini Augusti
Apr 25, 2020·Antioxidants·Sara DamianoRoberto Ciarcia
Feb 6, 2021·Archives of Toxicology·Hu LiXingxiang Chen

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