RESUMO
Vascular endothelial growth factor (VEGF) exerts both neuroprotective and proinflammatory effects in the brain, depending on the VEGF (A-E) and VEGF receptor (VEGFR1-3) types involved. Neonatal monosodium glutamate (MSG) treatment triggers an excitotoxic degenerative process associated with several neuropathological conditions, and VEGF messenger RNA (mRNA) expression is increased at postnatal day (PD) 14 in rat hippocampus (Hp) following the treatment. The aim of this work was to establish the changes in immunoreactivity to VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 proteins induced by neonatal MSG treatment (4 g/kg, subcutaneous, at PD1, 3, 5 and 7) in the cerebral motor cortex (CMC) and Hp. Samples collected from PD2 to PD60 from control and MSG-treated male Wistar rats were assessed by western blotting for each protein. Considering that immunoreactivity measured by western blotting is related to the protein expression level, we found that each protein in each cerebral region has a specific expression profile throughout the studied ages, and all profiles were differentially modified by MSG. Specifically, neonatal MSG treatment significantly increased the immunoreactivity to the following: (1) VEGF-A at PD8-PD10 in the CMC and at PD6-PD8 in the Hp; (2) VEGF-B at PD2, PD6 and PD10 in the CMC and at PD8-PD9 in the Hp; and (3) VEGFR-2 at PD6-PD8 in the CMC and at PD21-PD60 in the Hp. Also, MSG significantly reduced the immunoreactivity to the following: (1) VEGF-B at PD8-PD9 and PD45-PD60 in the CMC; and (2) VEGFR-1 at PD4-PD6 and PD14-PD21 in the CMC and at PD4, PD9-PD10 and PD60 in the Hp. Our results indicate that VEGF-mediated signalling is involved in the excitotoxic process triggered by neonatal MSG treatment and should be further characterized.
Assuntos
Ácido Glutâmico/toxicidade , Hipocampo/efeitos dos fármacos , Córtex Motor/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator B de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Masculino , Córtex Motor/crescimento & desenvolvimento , Córtex Motor/metabolismo , Ratos , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/genética , Fator B de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
INTRODUCTION: Angiogenesis is essential for the local growth, invasion and metastasis of the tumours. Vascular endothelial growth factors (VEGFs) play a crucial role in tumour angiogenesis. The aim of our study was to quantify the expression of several VEGF family molecules in human gastro-oesophageal cancers and to analyse possible correlations between genes expression and clinico-pathological features. MATERIALS AND METHODS: Gene expression was quantified in 43 gastro-oesophageal paired samples using qRT-PCR with TaqMan probes specific to VEGF-A, including soluble transcript variants and VEGF-B genes. RESULTS: VEGF-A, including the studied splice variants and VEGF-B mRNAs were expressed in both tumour and peritumour mucosa. The expression of VEGF-A and its isoforms was higher in tumour compared with paired peritumour mucosa, while no significant difference was observed in VEGF-B expression. VEGF-A expression tended to correlate with tumour invasion. CONCLUSION: VEGF-A has a tendency to over-express in gastro-oesophageal cancers, while VEGF-B does not seem involved in these tumours. Further studies are required to establish the utility of anti-VEGF-A therapy and to find biomarkers for pathogenesis or response to therapy in gastro-oesophageal tumours.