Pharmacological inhibition of heparin-binding EGF-like growth factor promotes peritoneal angiogenesis in a peritoneal dialysis rat model.
Clin Exp Nephrol
; 22(2): 257-265, 2018 Apr.
Article
em En
| MEDLINE
| ID: mdl-28710535
ABSTRACT
BACKGROUND:
Molecular mechanisms of peritoneal dialysis (PD) ultrafiltration failure, peritoneal neo-angiogenesis, and fibrosis remain to be determined. We aimed to determine the role of heparin-binding EGF-like growth factor (HB-EGF) inhibition on angiogenesis of peritoneal membrane in a PD rat model.METHODS:
32 male Wistar rats were assigned into (1) control group; (2) uremic non-PD group subtotal nephrectomy-induced uremic rats without PD; (3) uremic rats subjected to PD uremic rats that were dialyzed with Dianeal® for 4 weeks; (4) CRM 197 group dialyzed uremic rats were supplemented with CRM197, a specific HB-EGF inhibitor. Peritoneal transport function was examined by peritoneal equilibration test. Expression of HB-EGF and EGFR in peritoneal samples were examined by real-time PCR, immunohistochemical staining, and western blot.RESULTS:
Progressive angiogenesis and fibrosis were observed in uremic PD rats, and there were associated with decreased net ultrafiltration (nUF), increased permeability of peritoneal membrane, and reduced expression of HB-EGF and EGFR protein and mRNA in uremic PD rats compared to uremic non-PD or control groups (both p < 0.05). CRM197 significantly induced peritoneal membrane permeability, decreased nUF, increased higher vessel density, and reduced pericyte count compared to that of uremic PD rats. The levels of HB-EGF and EGFR expression negatively correlated with vessel density in peritoneal membrane (both p < 0.001).CONCLUSION:
PD therapy was associated with peritoneal angiogenesis, functional deterioration, and downregulation of HB-EGF/EGFR. Pharmacological inhibition of HB-EGF promoted PD-induced peritoneal angiogenesis and fibrosis and ultrafiltration decline, suggesting that HB-EGF downregulation contributes to peritoneal functional deterioration in the uremic PD rat model.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peritônio
/
Proteínas de Bactérias
/
Uremia
/
Indutores da Angiogênese
/
Fator de Crescimento Semelhante a EGF de Ligação à Heparina
/
Neovascularização Patológica
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article