Delidaki, Maria, Gu, Mei, Hein, Anna, Vatish, Manu and Grammatopoulos, Dimitris K.. (2011) Interplay of cAMP and MAPK pathways in hCG secretion and fusogenic gene expression in a trophoblast cell line. Molecular and Cellular Endocrinology, Vol.332 (No.1-2). pp. 213-220. ISSN 03037207

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Abstract

Differentiation of human placental mononuclear trophoblasts into a multinucleate syncytium involves up-regulation of key proteins promoting cell fusion and increased capacity for placental hormonogenesis. It is well established that the activation of adenylyl cyclase leads to increased expression of trophoblast fusogenic gene machinery and human chorionic gonadotropin (hCG) secretion. We used the forskolin-induced syncytialisation of BeWo choriocarcinoma cells as a model to characterise in detail the signalling pathway downstream of adenylyl cyclase. Forskolin treatment induced a rapid and potent ERK1/2 and p38MAPK phosphorylation; this cascade required PKA–AKAP interactions and led to downstream CREB-1/ATF-1 phosphorylation via ERK1/2-dependent but p38MAPK-independent mechanisms. Interestingly both p38MAPK and ERK1/2 were involved in forskolin-induced hCG-secretion, suggesting the presence of additional p38MAPK-dependent but CREB-1/ATF-1-independent pathways. Forskolin treatment of BeWo cells significantly up-regulated the expression of various fusogenic gene mRNAs, including syncytin-1 and -2 (by 3- and 10-fold, respectively) the transcription factors old astrocyte specifically induced substance (OASIS) and glial cells missing a (GCMa) (by 3- and 6-fold, respectively) and the syncytin-2 receptor, major facilitator superfamily domain containing 2 (MFSD2) (by 2-fold). Up-regulation of AKAP79 and AKAP250 (by 2.5- and 4-fold, respectively) was also identified in forskolin-treated BeWo cells. Forskolin effects on all these genes were suppressed by chemical inhibition of p38MAPK whereas only specific genes were sensitive to ERK1/2 inhibition. This data provide novel insights into the signalling molecules and mechanisms regulating fusogenic gene expression by the adenylyl cyclase pathway.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH426 Genetics Q Science > QP Physiology R Medicine > RC Internal medicine R Medicine > RG Gynecology and obstetrics
Divisions:	Faculty of Medicine > Warwick Medical School > Metabolic and Vascular Health Faculty of Medicine > Warwick Medical School > Reproductive Health Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Gene expression, Endocrine genetics, Obstetrical endocrinology, Placenta, Trophoblast
Journal or Publication Title:	Molecular and Cellular Endocrinology
Publisher:	Elsevier
ISSN:	03037207
Date:	30 January 2011
Volume:	Vol.332
Number:	No.1-2
Page Range:	pp. 213-220
Identification Number:	10.1016/j.mce.2010.10.013
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	WPH Charitable Trust, University of Warwick , UHCW NHS Trust
URI:	http://wrap.warwick.ac.uk/id/eprint/36505

Data sourced from Thomson Reuters' Web of Knowledge

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