Pigment epithelium-derived factor (PEDF): a novel trophoblast-derived factor limiting feto-placental angiogenesis in late pregnancy.

Angiogenesis 2016 07 8;19(3):373-88. Epub 2016 Jun 8.

Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria.

The rapidly expanding feto-placental vasculature needs tight control by paracrine and endocrine mechanisms. Here, we focused on paracrine influence by trophoblast, the placental epithelium. We aimed to identify differences in regulation of feto-placental angiogenesis in early versus late pregnancy. To this end, the effect of conditioned media (CM) from early and late pregnancy human trophoblast was tested on network formation, migration and proliferation of human feto-placental endothelial cells. Only CM of late pregnancy trophoblast reduced network formation and migration. Screening of trophoblast transcriptome for anti-angiogenic candidates identified pigment epithelium-derived factor (PEDF) with higher expression and protein secretion in late pregnancy trophoblast. Addition of a PEDF-neutralizing antibody restored the anti-angiogenic effect of CM from late pregnancy trophoblast. Notably, human recombinant PEDF reduced network formation only in combination with VEGF. Also in the CAM assay, the combination of PEDF with VEGF reduced branching of vessels below control levels. Analysis of phosphorylation of ERK1/2 and FAK, two key players in VEGF-induced proliferation and migration, revealed that PEDF altered VEGF signaling, while PEDF alone did not affect phosphorylation of ERK1/2 and FAK. These data suggest that the trophoblast-derived anti-angiogenic molecule PEDF is involved in restricting growth and expansion of the feto-placental endothelium predominantly in late pregnancy and targets to modulate the intracellular effect of VEGF.

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http://dx.doi.org/10.1007/s10456-016-9513-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930480PMC
July 2016
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References

(Supplied by CrossRef)

C Wadsack et al.
Wien Med Wochenschr 2012

DE Clark et al.
J Endocrinol 1998

DS Charnock-Jones et al.
J Anat 2002

D Ribatti et al.
Angiogenesis 2008

M Zygmunt et al.
Eur J Obstet Gynecol Reprod Biol 2003

SE Maynard et al.
J Clin Invest 2003

R Demir et al.
Placenta 2004

S Ahmad et al.
Circ Res 2004

RL Kendall et al.
Biochem Biophys Res Commun 1996

I Lang et al.
Eur J Cell Biol 2003

M Cervar et al.
Cell Tissue Res 1999

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