RGD Reference Report - Changes in fetal lung distension alter expression of vascular endothelial growth factor and its isoforms in developing rat lung. - Rat Genome Database
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Changes in fetal lung distension alter expression of vascular endothelial growth factor and its isoforms in developing rat lung.

Authors: Hara, A  Chapin, CJ  Ertsey, R  Kitterman, JA 
Citation: Hara A, etal., Pediatr Res. 2005 Jul;58(1):30-7. Epub 2005 May 5.
RGD ID: 7421593
Pubmed: (View Article at PubMed) PMID:15879288
DOI: Full-text: DOI:10.1203/01.PDR.0000163614.20031.C5

Vascular endothelial growth factor A (VEGF-A) is essential for normal pulmonary vascular and parenchymal development. Changes in fetal lung distension profoundly affect lung growth and maturation, including vascular development. To define developmental lung expression of VEGF-A and its receptors and investigate effects of changes in fetal lung distension, we studied fetal rats at embryonic day (ED) 16, 19, and 22, postnatal rats at postnatal day (PD) 5, 10, and 21, and adult rats. We used reverse transcriptase PCR to measure mRNA expression for VEGF-A isoforms (VEGF-A(120), (-144), (-164), and (-188)) and VEGF-A receptors, Flt-1 and Flk-1. With advancing development, mRNA content increased only for VEGF-A(188) (p < 0.05) and for Flt-1 (p < 0.02) and Flk-1 (p < 0.005). As a percentage of total VEGF-A mRNA, VEGF-A(188) (15% at ED 16) increased to become the dominant isoform at PD 21 (40%, p < 0.005) and adulthood; in contrast, there were decreases in both VEGF-A(144) (p < 0.05) and (-120) (p < 0.005). VEGF-A protein was expressed in alveolar epithelium (type I and II cells) and interstitium. Increasing fetal lung distension by tracheal occlusion (TO) accelerated the normal maturational pattern of VEGF-A isoforms and increased VEGF-A protein; decreasing fetal lung distension by congenital diaphragmatic hernia (CDH) retarded the normal developmental pattern and decreased VEGF-A protein. Neither TO nor CDH consistently affected Flt-1 or Flk-1 mRNA content. These results show that mechanical factors significantly affect lung VEGF-A expression and suggest that VEGF-A mediates previously described changes in lung vascular and parenchymal development caused by CDH and by TO.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Vegfa  (vascular endothelial growth factor A)

Genes (Mus musculus)
Vegfa  (vascular endothelial growth factor A)

Genes (Homo sapiens)
VEGFA  (vascular endothelial growth factor A)


Additional Information