Evidence for a Role of TGF-β1 in the Expression and Regulation of α-SMA in Fetal Growth Restricted Placentae

Todros, T.; Marzioni, D.; Lorenzi, T.; Piccoli, E.; Capparuccia, L.; Perugini, V.; Cardaropoli, S.; Romagnoli, R.; Gesuita, R.; Rolfo, A.; Paulesu, L.; Castellucci, M.

doi:10.1016/j.placenta.2007.06.003

« Previous Next »Placenta
Volume 28, Issue 11 , Pages 1123-1132, November 2007

Evidence for a Role of TGF-β1 in the Expression and Regulation of α-SMA in Fetal Growth Restricted Placentae

T. Todros
- Department of Obstetrics and Gynecology, University of Turin, 10126 Turin, Italy
- T. Todros and D. Marzioni equally contributed to this work as first authors.
D. Marzioni
- Institute of Normal Human Morphology, Faculty of Medicine, Polytechnic University of Marche, Via Tronto 10/a, 60020 Ancona, Italy
- Corresponding author. Tel.: +39 071 220 6081/6086; fax: +39 071 220 6087.
- T. Todros and D. Marzioni equally contributed to this work as first authors.
T. Lorenzi
- Institute of Normal Human Morphology, Faculty of Medicine, Polytechnic University of Marche, Via Tronto 10/a, 60020 Ancona, Italy
E. Piccoli
- Department of Obstetrics and Gynecology, University of Turin, 10126 Turin, Italy
L. Capparuccia
- Institute of Normal Human Morphology, Faculty of Medicine, Polytechnic University of Marche, Via Tronto 10/a, 60020 Ancona, Italy
V. Perugini
- Institute of Normal Human Morphology, Faculty of Medicine, Polytechnic University of Marche, Via Tronto 10/a, 60020 Ancona, Italy
S. Cardaropoli
- Department of Obstetrics and Gynecology, University of Turin, 10126 Turin, Italy
R. Romagnoli
- Department of Physiology, Division of Immunoendocrinology and Reproductive Physiology, University of Siena, 53100 Siena, Italy
R. Gesuita
- Centre of Epidemiology, Bio-statistic and Medical Information, Polytechnic University of Marche, 60020 Ancona, Italy
A. Rolfo
- Department of Obstetrics and Gynecology, University of Turin, 10126 Turin, Italy
L. Paulesu
- Department of Physiology, Division of Immunoendocrinology and Reproductive Physiology, University of Siena, 53100 Siena, Italy
M. Castellucci
- Institute of Normal Human Morphology, Faculty of Medicine, Polytechnic University of Marche, Via Tronto 10/a, 60020 Ancona, Italy

Accepted 8 June 2007. published online 03 August 2007.

Abstract

There is evidence that α-smooth muscle actin (α-SMA) is a protein that plays a pivotal role in the production of contractile forces and it is induced by transforming growth factor-β1 (TGF-β1). We have analysed the expression of α-SMA, TGF-β1, its receptor RI and the activator phospho-Smad2 in (a) fetal growth restriction pre-eclamptic placentae characterised by early onset and absence of end diastolic velocities in the umbilical arteries (FGR-AED) and (b) control placentae accurately matched for gestational age. The study was performed by immunohistochemical, quantitative Western blotting, ELISA, RT–PCR and in vitro analyses. We found that TGF-β1 stimulates α-SMA production in chorionic villi cultured in vitro. In addition, we observed that in vivo TGF-β1 concentration is significantly higher in FGR-AED placental samples than in control placentae and that this growth factor could have a paracrine action on villous stroma myofibroblasts expressing TGF-β1 receptors and phospho-Smad2. Indeed, we report that α-SMA undergoes a redistribution in FGR-AED placental villous tree, i.e. we show that α-SMA is enhanced in medium and small stem villi and significantly decreased in the peripheral villi. Our data allow us to consider TGF-β1 and α-SMA as key molecules related to FGR-AED placental villous tree phenotypic changes responsible for increased impedance to blood flow observable in this pathology.

Keywords: α-Smooth muscle actin, FGR-AED, Human placenta, Transforming growth factor-β1