Chorionic villous mesenchymal stem cell-derived exosomes promote trophoblasts proliferation and invasion through delivery miR-135b-5p targeting TXNIP via the β-catenin pathway

Human chorionic villous mesenchymal stem cells (CV-MSCs) are a promising and effective treatment for tissue injury. Trophoblast dysfunction during pregnancy is significantly involved in the pathogenesis of preeclampsia (PE). This work aimed to understand how CV-MSCs regulate trophoblast function. In this study, we treated trophoblasts with CV-MSC-derived exosomes, and RNA-seq analysis was used to understand the differences in trophoblasts induced by exosomes. We examined the levels of TXNIP (thioredoxin-interactingprotein) and β-catenin in trophoblasts by immunohistochemistry, western blotting and qRT-PCR assays. Luciferase reporter assays and qRT-PCR assays were used to examine the role of miR135 b-5p in the effects of CV-MSC-derived exosomes. The growth and invasion of trophoblasts was evaluated using CCK-8 and Transwell assays. CV-MSC-derived exosomes markedly enhanced trophoblast proliferation and invasion. Furthermore, a significant decrease in TXNIP expression and activation of the β-catenin pathway in CV-MSC exosome-treated trophoblasts were observed. Consistent with these findings, TXNIP inhibition promoted trophoblast proliferation and invasion, similar to the effect of CV-MSC-derived exosomes, and this effect was accompanied by activation of the β-catenin pathway. In addition, overexpression of TXNIP inactivated the β-catenin pathway in trophoblasts and reduced the proliferation and invasion of trophoblasts. Importantly, miR135 b-5p was highly expressed in CV-MSC exosomes and interacted with TXNIP. MiR-135 b-5p overexpression significantly increased the proliferation and invasion of trophoblasts, which was attenuated by TXNIP overexpression. Our results suggest that TXNIP-dependent β-catenin pathway activation mediated by miR-135 b-5p, which was delivered by CV-MSC-derived exosomes, could promote the proliferation and invasion of trophoblasts.

CV-MSCs; TXNIP; Trophoblasts; miR-135 b-5p; β-catenin.