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

Nicoletta Gagliano, Carlo Torri, Elena Donetti, Fabio Grizzi, Francesco Costa, Alberto A E Bertelli, Massimiliano Migliori, Cristina Filippi, Marzia Bedoni, Vincenzo Panichi, Luca Giovannini, Magda Gioia

Research output: Contribution to journalArticle

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 α-smooth muscle actin (αSMA), 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-β1 signaling tended to dominate after OTA, OTA-wine, and OTA-EtOH. MMP-1 protein levels were not affected. OTA induced proMMP-9 and αSMA overexpression, decreases of E-cadherin and N-cadherin, and DSC-2 up-regulation. OTA-wine caused a further, unexpected decrease of E- and N-cadherins and further up-regulation of OTA-induced DSC-2, while strongly reducing the OTA-induced increases of αSMA and proMMP-9. Posttranslational collagen modifications, such as decreased collagen degradation through MMP inhibition and increased collagen cross-links, seem to be key mechanisms leading to OTA-induced kidney cortex fibrosis. This mechanism was not affected by red wine in these conditions. Red wine seems to have some protective role against OTA-induced EMT, although without completely blocking the process and determining a condition in which abundant cells display an intermediate translational phenotype, but there are no αSMA or epithelial markers.

Original languageEnglish
Pages (from-to)30-38
Number of pages9
JournalMolecular medicine (Cambridge, Mass.)
Volume11
Issue number1-12
DOIs
Publication statusPublished - Jan 2005

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Ochratoxin A-induced renal cortex fibrosis and epithelial-to-mesenchymal transition: Molecular mechanisms of ochratoxin A-injury and potential effects of red wine'. Together they form a unique fingerprint.

  • Cite this