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

Loegl J, Nussbaumer E, Hiden U, Majali-Martinez A, Ghaffari-Tabrizi-Wizy N, Cvitic S, Lang I, Desoye G, Huppertz B - Angiogenesis (2016)

Bottom Line: Notably, human recombinant PEDF reduced network formation only in combination with VEGF.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Anti-angiogenic activity of the combination of PEDF and VEGF on vessel formation of the chorioallantoic membrane (CAM). The same CAMs were treated with on-plants (silicone rings) containing 10 ng/ml PEDF with 25 ng/ml VEGF and control on-plants. Representative pictures of each condition immediately after application of the silicone ring on day 0 and at day 4 of the treatments are shown. After 4 days the vessel structure shows tertiary and quaternary vessels (white arrows). Addition of PEDF or VEGF alone did not affect vessel formation. Treatment with the combination of PEDF and VEGF CAM showed decreased angiogenesis by formation of fewer tertiary and quaternary vessels (white arrows)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4930480&req=5

Fig5: Anti-angiogenic activity of the combination of PEDF and VEGF on vessel formation of the chorioallantoic membrane (CAM). The same CAMs were treated with on-plants (silicone rings) containing 10 ng/ml PEDF with 25 ng/ml VEGF and control on-plants. Representative pictures of each condition immediately after application of the silicone ring on day 0 and at day 4 of the treatments are shown. After 4 days the vessel structure shows tertiary and quaternary vessels (white arrows). Addition of PEDF or VEGF alone did not affect vessel formation. Treatment with the combination of PEDF and VEGF CAM showed decreased angiogenesis by formation of fewer tertiary and quaternary vessels (white arrows)

Mentions: The combined effect of PEDF and VEGF was also tested in CAM assays. Similar to the 2D network formation, the combined application of PEDF and VEGF reduced formation of tertiary and quaternary vessels after 4 days of treatment (Fig. 5), while PEDF and VEGF alone had no effect.Fig. 5


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

Loegl J, Nussbaumer E, Hiden U, Majali-Martinez A, Ghaffari-Tabrizi-Wizy N, Cvitic S, Lang I, Desoye G, Huppertz B - Angiogenesis (2016)

Anti-angiogenic activity of the combination of PEDF and VEGF on vessel formation of the chorioallantoic membrane (CAM). The same CAMs were treated with on-plants (silicone rings) containing 10 ng/ml PEDF with 25 ng/ml VEGF and control on-plants. Representative pictures of each condition immediately after application of the silicone ring on day 0 and at day 4 of the treatments are shown. After 4 days the vessel structure shows tertiary and quaternary vessels (white arrows). Addition of PEDF or VEGF alone did not affect vessel formation. Treatment with the combination of PEDF and VEGF CAM showed decreased angiogenesis by formation of fewer tertiary and quaternary vessels (white arrows)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4930480&req=5

Fig5: Anti-angiogenic activity of the combination of PEDF and VEGF on vessel formation of the chorioallantoic membrane (CAM). The same CAMs were treated with on-plants (silicone rings) containing 10 ng/ml PEDF with 25 ng/ml VEGF and control on-plants. Representative pictures of each condition immediately after application of the silicone ring on day 0 and at day 4 of the treatments are shown. After 4 days the vessel structure shows tertiary and quaternary vessels (white arrows). Addition of PEDF or VEGF alone did not affect vessel formation. Treatment with the combination of PEDF and VEGF CAM showed decreased angiogenesis by formation of fewer tertiary and quaternary vessels (white arrows)
Mentions: The combined effect of PEDF and VEGF was also tested in CAM assays. Similar to the 2D network formation, the combined application of PEDF and VEGF reduced formation of tertiary and quaternary vessels after 4 days of treatment (Fig. 5), while PEDF and VEGF alone had no effect.Fig. 5

Bottom Line: Notably, human recombinant PEDF reduced network formation only in combination with VEGF.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus