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Biology of Reproduction 60, 887-892 (1999)
©Copyright 1999 Society for the Study of Reproduction, Inc.

Signal Transduction and Biological Function of Placenta Growth Factor in Primary Human Trophoblast1

Jaya Desaia, Vicky Holt-Shorea, Ronald J. Torryb, Michael R. Caudlea, and Donald S. Torry2,a

a Department of Obstetrics and Gynecology, University of Tennessee Graduate School of Medicine, Knoxville, Tennessee 37922 b Methodist Research Institute, Clarian Health, Indianapolis, Indiana 46202

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 {gamma} and tumor necrosis factor {alpha}. 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.

1 Supported in part by the American Heart Association Southeast Affiliate (D.S.T.), Physicians Medical Education and Research Foundation, Knoxville, TN (D.S.T.), and the American Heart Association Indiana Affiliate (R.J.T.).

2 Correspondence: Donald S. Torry, Department of OB/GYN, University of Tennessee Graduate School of Medicine, Box U-27, 1924 Alcoa Highway, Knoxville, TN 37922. FAX: 423 544 6822; dtorry{at}utk.edu




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