Signal transduction and biological function of placenta growth factor in primary human trophoblast

Jaya Desai, Vicky Holt-Shore, Ronald J. Torry, Michael Caudle, Donald S. Torry

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Placenta growth factor (PIGF), 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 PIGF 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 PIGF. Exogenous PIGF 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, PIGF induced significant ERK-1 and -2 activity in human umbilical vein endothelial cells but did not induce JNK or p38 activity. PIGF-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 γ. These results provide the first direct evidence of a biochemical and functional role for PIGF/Flt-1 in normal trophoblast and suggest that aberrant PIGF expression during pregnancy may impact upon trophoblast function as well as vascularity within the placental bed.

Original languageEnglish (US)
Pages (from-to)887-892
Number of pages6
JournalBiology of Reproduction
Volume60
Issue number4
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

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Trophoblasts
Signal Transduction
Angiogenesis Inducing Agents
Heat-Shock Proteins
Protein Kinases
Placenta Growth Factor
MAP Kinase Kinase 4
Apoptosis
Mitogen-Activated Protein Kinase 3
JNK Mitogen-Activated Protein Kinases
Human Umbilical Vein Endothelial Cells
Endometrium
Interferons
Placenta
Vascular Endothelial Growth Factor A
Intercellular Signaling Peptides and Proteins
Tumor Necrosis Factor-alpha
Cytokines
Pregnancy

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Signal transduction and biological function of placenta growth factor in primary human trophoblast. / Desai, Jaya; Holt-Shore, Vicky; Torry, Ronald J.; Caudle, Michael; Torry, Donald S.

In: Biology of Reproduction, Vol. 60, No. 4, 01.01.1999, p. 887-892.

Research output: Contribution to journalArticle

Desai, Jaya ; Holt-Shore, Vicky ; Torry, Ronald J. ; Caudle, Michael ; Torry, Donald S. / Signal transduction and biological function of placenta growth factor in primary human trophoblast. In: Biology of Reproduction. 1999 ; Vol. 60, No. 4. pp. 887-892.
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