Mol. Hum. Reprod. Advance Access published online on December 9, 2005
Molecular Human Reproduction, doi:10.1093/molehr/gah242
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1 Division of Clinical Chemistry, Institute of Genetics, School of Molecular Medical Sciences, University Hospital, Nottingham
* To whom correspondence should be addressed. The angiotensin II type 1 (AT1) receptor, transforming growth factor
Received August 10, 2005
Revised October 21, 2005
Accepted October 26, 2005
Article
Transforming growth factor
C.L. Tower 1,
S.L. Chappell 1,
K. Morgan 1,
N. Kalsheker 1,
P.N. Baker 2,
and
L.J. Morgan 1 *
1 regulates angiotensin II type I receptor gene expression in the extravillous trophoblast cell line SGHPL-4
2 Maternal and Fetal Health Research Centre, St. Mary’s Hospital, Whitworth Park, Manchester, UK
L.J. Morgan, E-mail: linda.morgan{at}nottingham.ac.uk
Abstract 
1 (TGF1) and Oncostatin M (OSM) control key pathways that may be important during placentation. Although interactions between them exist in other tissues, trophoblast cells have not been investigated. Extravillous trophoblast cells, SGHPL-4, were stimulated with 10 ng/ml TGF1 ± 100 ng/ml OSM for 24 h. Real-time PCR showed that AT1 expression increased 2.76-fold [95% confidence interval (CI) = 1-6.74, P = 0.05] in response to TGF1 and 4.21-fold (95% CI = 1.33-11.76, P = 0.03) with TGF1 + OSM. Luciferase reporter gene constructs containing three haplotypes of the 5' flanking region of the AT1 receptor gene were transfected into SGHPL-4 and HepG2 cells and stimulated with 0.1, 1 and 10 ng/ml TGF1 and 50 ng/ml OSM. Responses were dose and cell dependent. Luciferase activity increased in HepG2 cells in response to TGF1 alone or together with OSM (P < 0.001); transcriptional activation differed between AT1 receptor gene haplotypes. In SGHPL-4 cells, luciferase activity was reduced on exposure to low concentrations of TGF1 or high concentrations of TGF1 combined with OSM (P = 0.003); the response was unaffected by haplotype. Interaction between AT1 and TGF1 is a novel observation in trophoblast and suggests new avenues for the study of placentation.1/trophoblast.
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