Amphotericin B-copper (II) complex alters transcriptional activity of genes encoding transforming growth factor-beta family members and related proteins in renal cells.
Pharmacol Rep
; 69(6): 1308-1314, 2017 Dec.
Article
em En
| MEDLINE
| ID: mdl-29128814
ABSTRACT
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-ß). 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-ß 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-ß family members and related genes was determined using oligonucleotide microarrays. TGF-ß1 protein level was determined using ELISA method. The mRNA level of TGF-ß isoforms, TGF-ß receptors and differentiating genes was evaluated by real-time RT-qPCR.RESULTS:
AmB-Cu2+ increased the mRNA levels of TGF-ß1 and TGF-ß2 isoforms and two genes encoding receptors TGFBR1 and TGFBR2. TGF-ß1 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anfotericina B
/
Fator de Crescimento Transformador beta
/
Cobre
/
Túbulos Renais Proximais
Limite:
Humans
Idioma:
En
Revista:
Pharmacol Rep
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de publicação:
CH
/
SUIZA
/
SUÍÇA
/
SWITZERLAND