Hoxb-5 down regulation alters Tenascin-C, FGF10 and Hoxb gene expression patterns in pseudoglandular period fetal mouse lung.
Front Biosci
; 12: 860-73, 2007 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-17127343
ABSTRACT
Organ-specific patterning is partly determined by Hox gene regulatory interactions with the extracellular matrix (ECM), cell adhesion and fibroblast growth factor (FGFs) signaling pathways but coordination of these mechanisms in lung development is unknown. We have previously shown that Hoxb-5 affects airway patterning during lung morphogenesis. Hoxb-5 regulation in fetal lung affects ECM expression of tenascin-C and alters FGF10 spatial and cellular expression. To test this hypothesis, gestational day 13.5 (Gd13.5) fetal mouse lung fibroblasts and whole lungs were cultured with Hoxb-5-specific small interfering RNA (siRNA). Western blots showed that siRNA-down regulation of Hoxb-5 led to decreased tenascin-C and FGF10 and was associated with increased Hoxb-4 and decreased Hoxb-6 protein levels. Hoxa-5 protein levels were not affected. Hoxb-5 siRNA-treated whole lung cultures had a significant decrease in total lung and peripheral branching region surface area. Immunostaining showed negligible levels of Hoxb-5 protein and tenascin-C, and loss of FGF10 spatial restriction. We conclude that Hoxb-5 helps regulate lung airway development through modulation of ECM expression of tenascin-C. ECM changes induced by Hoxb-5 may affect mesenchymal-epithelial cell signaling to alter spatial and cellular restriction of FGF10. Hoxb-5 may also affect lung airway branching indirectly by cross regulation of other Hoxb genes.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Homeodomínio
/
Tenascina
/
Fator 10 de Crescimento de Fibroblastos
/
Pulmão
Limite:
Animals
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article