Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Matrix metalloproteinases (MMPs) play crucial roles in extravillous trophoblast invasion. In the present study, we examined the possible role of Smad4 and Smad2 in transforming growth factor (TGF)-beta1-induced MMP-2 expression, using the well-established invasive extravillous trophoblast cell line HTR-8/SVneo. Recombinant sense Smad4 or Smad2 retroviral vectors were constructed by inserting full-length Smad4 or Smad2 cDNA into pLXSN retroviral vector. Stable PT67 packaging cell clones were isolated and viral supernatants were used to infect HTR-8/SVneo cells. Effects of retroviral expression of Smad4 and Smad2 on TGF-beta1-regulated MMP-2 expression were assessed by semi-quantitative reverse transcription-polymerase chain reaction and gelatin zymography. The results showed that over-expression of Smad4 augmented MMP-2 mRNA abundance and the secretion of pro-MMP-2, and mimicked the inductive effect of TGF-beta1 on the production of MMP-2. However, retrovirus-mediated sense Smad2 gene transfer had no effect. These findings suggest that Smad4, but not Smad2, mediates TGF-beta1-induced MMP-2 expression in invasive extravillous trophoblasts.