RGD Reference Report - Bone morphogenetic protein 4 mediates apoptosis of capillary endothelial cells during rat pupillary membrane regression. - Rat Genome Database

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Bone morphogenetic protein 4 mediates apoptosis of capillary endothelial cells during rat pupillary membrane regression.

Authors: Kiyono, M  Shibuya, M 
Citation: Kiyono M and Shibuya M, Mol Cell Biol. 2003 Jul;23(13):4627-36.
RGD ID: 8998993
Pubmed: PMID:12808102   (View Abstract at PubMed)
PMCID: PMC164857   (View Article at PubMed Central)

Programmed capillary regression is essential for development, but little is known about the mechanism behind this phenomenon. In this study, we characterized the molecular determinants of capillary regression utilizing the pupillary membrane (PM) in the newborn rat's eye. We observed in the 1-day-culture system that apoptotic endothelial cells decrease in number with the addition of a natural antagonist, Noggin, strongly suggesting the involvement of the bone morphogenetic protein (BMP) family in PM regression. In addition, the lens-conditioned medium (Lens-CM) induced apoptosis of HUVE cells and inhibited endothelial tubulogenesis, which were completely blocked by both Noggin and the BMP4-specific neutralizing antibody. Activation of BMP4 pathway in endothelial cells was confirmed by both the up-regulation of Msx genes correlated with apoptosis and the translocation of Smad1 into the nucleus. We showed a transient expression of BMP4 in Lens-CM by immunoprecipitation assay. Furthermore, the transcorneal injection of BMP4 in rats enhanced the apoptosis of PMs, while that of Noggin attenuated it. These results indicate that BMP4 pathways play pivotal roles in capillary regression in a paracrine manner between lens and PMs.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
anatomical structure regression  IEP 8998993 RGD 
positive regulation of endothelial cell apoptotic process  IMP 8998993 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bmp4  (bone morphogenetic protein 4)


Additional Information