Signal Transduction and Biological Function of Placenta Growth Factor in Primary Human Trophoblast

• Published in: Biology of reproduction 1999-04, Vol.60 (4), p.887-892
• Main Authors: DESAI, J, HOLT-SHORE, V, TORRY, R. J, CAUDLE, M. R, TORRY, D. S
• Format: Article
• Language: English
• Subjects: Apoptosis; Biological and medical sciences; Cells, Cultured; Embryology: invertebrates and vertebrates. Teratology; Female; Fetal membranes; Fundamental and applied biological sciences. Psychology; General aspects. Development. Fetal membranes; Humans; Interferon-gamma - pharmacology; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase 4; Mitogen-Activated Protein Kinase Kinases; Placenta Growth Factor; Pregnancy; Pregnancy Proteins - pharmacology; Pregnancy Proteins - physiology; Protein Kinases - metabolism; Proto-Oncogene Proteins - analysis; Receptor Protein-Tyrosine Kinases - analysis; Signal Transduction; Trophoblasts - chemistry; Trophoblasts - physiology; Tumor Necrosis Factor-alpha - pharmacology; Vascular Endothelial Growth Factor Receptor-1
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod60.4.887

Placenta growth factor (PlGF), a member of the vascular endothelial growth factor family of angiogenic factors, is prominently expressed by trophoblast. In addition to its role as a paracrine angiogenic factor within the placenta and endometrium, presence of its receptor, Flt-1, on trophoblast suggests that PlGF also may have an autocrine role(s) in regulating trophoblast function. To elucidate its role in trophoblast, we examined the signal transduction and functional responses of primary human trophoblast to PlGF. Exogenous PlGF induced specific activation of the stress-activated protein kinase (SAPK) pathways, c-Jun-N terminal kinase (JNK) and p38 kinase, in primary term trophoblast with little to no induction of the extracellular signal regulated kinase (ERK-1 and -2) pathways. In contrast, PlGF induced significant ERK-1 and -2 activity in human umbilical vein endothelial cells but did not induce JNK or p38 activity. PlGF-induced activation of the SAPK signaling pathways protected trophoblast from growth factor withdrawal-induced apoptosis, but it did not protect trophoblast from apoptosis induced by the pro-inflammatory cytokines, interferon γ and tumor necrosis factor α. These results provide the first direct evidence of a biochemical and functional role for PlGF/Flt-1 in normal trophoblast and suggest that aberrant PlGF expression during pregnancy may impact upon trophoblast function as well as vascularity within the placental bed.