Mol. Hum. Reprod. Advance Access originally published online on December 9, 2005
Molecular Human Reproduction 2005 11(12):847-852; doi:10.1093/molehr/gah242
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Transforming growth factor ß1 regulates angiotensin II type I receptor gene expression in the extravillous trophoblast cell line SGHPL-4
1Division of Clinical Chemistry, Institute of Genetics, School of Molecular Medical Sciences, University Hospital, Nottingham and 2Maternal and Fetal Health Research Centre, St. Mary’s Hospital, Whitworth Park, Manchester, UK
3 To whom correspondence should be addressed at: Clinical Chemistry, A Floor West Block, University Hospital, Nottingham NG7 2UH, UK. E-mail: linda.morgan{at}nottingham.ac.uk
The angiotensin II type 1 (AT1) receptor, transforming growth factor ß1 (TGFß1) 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 TGFß1 ± 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 TGFß1 and 4.21-fold (95% CI = 1.33–11.76, P = 0.03) with TGFß1 + OSM. Luciferase reporter gene constructs containing three haplotypes of the 59 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 TGFß1 and 50 ng/ml OSM. Responses were dose and cell dependent. Luciferase activity increased in HepG2 cells in response to TGFß1 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 TGFß1 or high concentrations of TGFß1 combined with OSM (P = 0.003); the response was unaffected by haplotype. Interaction between AT1 and TGFß1 is a novel observation in trophoblast and suggests new avenues for the study of placentation.
Key words: angiotensin type 1 receptor gene/gene regulation/transforming growth factor ß1/trophoblast
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