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

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.