PRR11 Regulates Proliferation, Migration and Angiogenesis of Human Trophoblasts by Activating EGR1-Mediated TGF-β/Smad Pathway

Abstract

Background: Proline-rich protein 11 (PRR11) is moderately expressed in the placenta and dysregulated in women with idiopathic recurrent pregnancy loss. The study aims to assess the role of PRR11 in early pregnancy loss (EPL). Methods: The in vivo expression of PRR11 in chorionic villi of patients with EPL was evaluated using immunohistochemistry, western blotting, and Quantitative Reverse Transcription PCR (qRT-PCR). The in vitro effects of PRR11 on proliferation, apoptosis, migration and angiogenesis of human first-trimester extravillous trophoblast cell line (HTR-8/SVneo) were determined using 2,5-diphenyl-2H-tetrazolium bromide (MTT), flow cytometry, Transwells, and tube formation assays. Results: PRR11 was reduced in in vivo chorionic villi of patients with EPL. PRR11 over-expression enhanced cell proliferation, while silencing of PRR11 promoted apoptosis of HTR-8/SVneo. Migration and angiogenesis of HTR-8/SVneo were promoted by PRR11. Early growth response protein 1 (EGR1), which positively correlated with PRR11, was also down-regulated in chorionic villi of patients with EPL. Knockdown of EGR1 attenuated PRR11 over-expression-induced up-regulation of transforming growth factor-beta 1 (TGF-β1), p-mothers against decapentaplegic homolog 2 (Drosophila) (p-Smad2) and p-Smad3, and EGR1 attenuated PRR11 silencing-induced down-regulation of TGF-β1, p-Smad2 and p-Smad3. Conclusion: PRR11 increased EGR1 and promoted the activation of TGF-β/Smad to facilitate proliferation, migration and angiogenesis of HTR-8/SVneo.