Journal
PLACENTA
Volume 30, Issue 10, Pages 907-913Publisher
W B SAUNDERS CO LTD
DOI: 10.1016/j.placenta.2009.07.003
Keywords
Endothelial cell; Signaling transduction; Placenta
Funding
- NHLBI NIH HHS [R01 HL087144, R01 HL070562, HL74947, R01 HL064703-08, R01 HL064703, HL70562, HL64703, R01 HL049210, HL87144, HL49210, R01 HL074947] Funding Source: Medline
- NICHD NIH HHS [HD38843, P01 HD038843-089003, P01 HD038843] Funding Source: Medline
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Vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) elicit cellular responses via activation of protein kinases and phosphatases. We have reported that the MEK1/2/ERK1/2 and PI3K/AKT1 pathways are critical for VEGF- and FGF2-stimulated ovine fetoplacental artery endothelial (OFPAE) cell proliferation. We have also shown that protein phosphatase 3 (PPP3) differentially modulates VEGF- and FGF2-stimulated cell proliferation and activation of ERK1/2 and AKT1 in OFPAE cells. Herein, we investigated if protein phosphatase 2 (PPP2) modulated VEGF- and FGF2-induced ERK1/2, AKT1, and p38 MAPK activation and VEGF- and FGF2-stimulated cell proliferation in OFPAE cells. Small interfering RNA (siRNA) specifically targeting human PPP2CA catalytic subunit a (PPP2CA) was used to suppress PPP2CA expression in OFPAE cells. When compared with scrambled siRNA, PPP2CA siRNA decreased (p < 0.05) PPP2CA protein levels (similar to 70%) and activity (similar to 50%) without altering protein levels of PPP3 catalytic subunit alpha (PPP3CA), nitric oxide synthase 3 (NOS3), ERK1/2, AKT1, and p38 MAPK. FGF2, but not VEGF rapidly (<= 5 min) induced p38 MAPK phosphorylation. Suppression of PPP2CA enhanced (p < 0.05) VEGF-induced AKT1, but not ERK1/2 phosphorylation, whereas inhibited (p < 0.05) FGF2-induced ERK1/2 and p38 MAPK and slightly attenuated FGF2-induced AKT1 phosphorylation. Suppression of PPP2CA did not significantly affect VEGF- and FGF2-stimulated OFPAE cell proliferation. Thus, suppression of PPP2CA alone differentially modulated VEGF- and FGF2-induced ERK1/2, AKT1, and p38 MAPK activation, without altering VEGF- and FGF2-stimulated cell proliferation in OFPAE cells. These data also suggest that signaling molecules other than ERK1/2, AKT1, and p38 MAPK are important mediators for VEGF- and FGF2-stimulated OFPAE cell proliferation after PPP2CA suppression. Published by Elsevier Ltd.
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