VEGF receptor expression decreases during lung development in congenital diaphragmatic hernia induced by nitrofen

Autor(es)

L. Sbragia ^[1] ; A.C.C. Nassr ^[2] ; F.L.L. Gonçalves ^[3] ; A.F. Schmidt ^[4] ; C.C. Zuliani ^[5] ; P.V. Garcia ^[6] ; R.M. Gallindo ^[1] ; L.A.V. Pereira ^[6]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Div Cirurgia Pediat, Dept Cirurgia & Anat, Fac Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Fed Sao Carlos, Dept Hidrobiol, Ctr Ciencias Biol & Saude, BR-13560 Sao Carlos, SP - Brazil

^[3] Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Cirurgia e Anatomia - Brasil

^[4] Cincinnati Childrens Hosp Med Ctr, Pediat House Off, Cincinnati, OH 45229 - USA

^[5] Univ Estadual Campinas, Fac Ciencias Med, Dept Clin Med, Campinas, SP - Brazil

^[6] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Histol & Embriol, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Medical and Biological Research; v. 47, n. 2, p. 171-178, 2014-02-00.

Resumo

Changes in vascular endothelial growth factor (VEGF) in pulmonary vessels have been described in congenital diaphragmatic hernia (CDH) and may contribute to the development of pulmonary hypoplasia and hypertension; however, how the expression of VEGF receptors changes during fetal lung development in CDH is not understood. The aim of this study was to compare morphological evolution with expression of VEGF receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1), in pseudoglandular, canalicular, and saccular stages of lung development in normal rat fetuses and in fetuses with CDH. Pregnant rats were divided into four groups (n=20 fetuses each) of four different gestational days (GD) 18.5, 19.5, 20.5, 21.5: external control (EC), exposed to olive oil (OO), exposed to 100 mg nitrofen, by gavage, without CDH (N-), and exposed to nitrofen with CDH (CDH) on GD 9.5 (term=22 days). The morphological variables studied were: body weight (BW), total lung weight (TLW), left lung weight, TLW/BW ratio, total lung volume, and left lung volume. The histometric variables studied were: left lung parenchymal area density and left lung parenchymal volume. VEGFR1 and VEGFR2 expression were determined by Western blotting. The data were analyzed using analysis of variance with the Tukey-Kramer post hoc test. CDH frequency was 37% (80/216). All the morphological and histometric variables were reduced in the N- and CDH groups compared with the controls, and reductions were more pronounced in the CDH group (P<0.05) and more evident on GD 20.5 and GD 21.5. Similar results were observed for VEGFR1 and VEGFR2 expression. We conclude that N- and CDH fetuses showed primary pulmonary hypoplasia, with a decrease in VEGFR1 and VEGFR2 expression. (AU)

• Processo FAPESP: 08/52772-9 - Efeito do acido retinoico sobre a expressao de receptores de vegf pulmonares em modelos animais de hernia diafragmatica congenita induzida por nitrofen.
• Beneficiário: Augusto Frederico Santos Schmidt
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 11/00794-1 - Avaliação da via do óxido nítrico in vivo após a oclusão traqueal fetal sobre a expressão de receptores de VEGF pulmonar na hérnia diafragmática congênita em ratos induzida pelo Nitrofen
• Beneficiário: Lourenço Sbragia Neto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/12587-0 - Avaliação in vivo do efeito do corticóide e da ventilação na via do óxido nítrico sobre a expressão do VEGF e seus receptores pulmonares após a oclusão traqueal fetal na hérnia diafragmática congênita em ratos
• Beneficiário: Frances Lilian Lanhellas Gonçalves
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 08/50347-9 - Efeito do ácido retinoico e sua interação com a traqueo-oclusão fetal sobre a expressão de receptores de VEGF pulmonar na hérnia diafragmática em ratos
• Beneficiário: Lourenço Sbragia Neto
• Modalidade de apoio: Auxílio à Pesquisa - Regular