Amphotericin B–copper (II) complex alters transcriptional activity of genes encoding transforming growth factor-beta family members and related proteins in renal cells

Background several chemical modifications have been developed to overcome the toxicity of amphotericin b (amb). oxidized forms of amb (amb-ox),which may occur in patient's circulation during therapy,are as toxic as amb. complexes with copper (ii) ions (amb–cu2+) have been reported to be less toxic to human cells. previous studies showed that amb changed the expression of transforming growth factor-beta (tgf-β). therefore,the objective of this study was to investigate the influence of amb and its modified forms on the expression of genes encoding for tgf-β family members and related proteins in renal cells. methods human renal proximal tubule cells (rptec) were treated with amb–cu2+,amb,or the oxidized form amb–ox. the expression of tgf-β family members and related genes was determined using oligonucleotide microarrays. tgf-β1 protein level was determined using elisa method. the mrna level of tgf-β isoforms,tgf-β receptors and differentiating genes was evaluated by real-time rt-qpcr. results amb–cu2+ increased the mrna levels of tgf-β1 and tgf-β2 isoforms and two genes encoding receptors: tgfbr1 and tgfbr2. tgf-β1 protein level in culture medium was not increased after stimulation with amb–cu2+. microarray analysis revealed changes in both pro-fibrotic and anti-fibrotic genes. conclusions these results suggest that amb–cu2+ may induce repair mechanisms in renal proximal tubule cells via changes in the expression of genes involved in intracellular signaling. © 2017 institute of pharmacology,polish academy of sciences