Neonatal vascularization and oxygen tension regulate appropriate perinatal renal medulla/papilla maturation.
J Pathol
; 238(5): 665-76, 2016 Apr.
Article
en En
| MEDLINE
| ID: mdl-26800422
ABSTRACT
Congenital medullary dysplasia with obstructive nephropathy is a common congenital disorder observed in paediatric patients and represents the foremost cause of renal failure. However, the molecular processes regulating normal papillary outgrowth during the postnatal period are unclear. In this study, transcriptional profiling of the renal medulla across postnatal development revealed enrichment of non-canonical Wnt signalling, vascular development, and planar cell polarity genes, all of which may contribute to perinatal medulla/papilla maturation. These pathways were investigated in a model of papillary hypoplasia with functional obstruction, the Crim1(KST264/KST264) transgenic mouse. Postnatal elongation of the renal papilla via convergent extension was unaffected in the Crim1(KST264/KST264) hypoplastic renal papilla. In contrast, these mice displayed a disorganized papillary vascular network, tissue hypoxia, and elevated Vegfa expression. In addition, we demonstrate the involvement of accompanying systemic hypoxia arising from placental insufficiency, in appropriate papillary maturation. In conclusion, this study highlights the requirement for normal vascular development in collecting duct patterning, development of appropriate nephron architecture, and perinatal papillary maturation, such that disturbances contribute to obstructive nephropathy.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Oxígeno
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Anomalías Urogenitales
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Reflujo Vesicoureteral
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Hipoxia Fetal
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Médula Renal
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Neovascularización Patológica
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Pathol
Año:
2016
Tipo del documento:
Article