Activation of the Hippo/TAZ pathway is required for menstrual stem cells to suppress myofibroblast and inhibit transforming growth factor β signaling in human endometrial stromal cells

作者：Haiyan Zhu, Yibin Pan, Yinshen Jiang, Jing Li, Yanling Zhang, Songying Zhang · 发表于：Human Reproduction · 年份：2019 · DOI：10.1093/humrep/dez001 · 被引用次数：71 · 研究领域：Uterine Myomas and Treatments、Reproductive System and Pregnancy、Angiogenesis and VEGF in Cancer

STUDY QUESTION: Can menstrual stem cells (MenSCs) inhibit myofibroblast differentiation and reverse transforming growth factor β (TGFβ)-mediated activation of myofibroblast phenotypes in human endometrial stromal cells (ESCs)? SUMMARY ANSWER: MenSCs suppressed endometrial myofibroblast differentiation and reversed TGFβ-mediated activation of myofibroblast phenotypes, which might be associated with activation of the Hippo/TAZ pathway. WHAT IS KNOWN ALREADY: The potential effect of MenSCs as a cell therapy include attenuation of intrauterine adhesions, but the underlying mechanisms by which MenSCs exerts these effects are not entirely understood. STUDY DESIGN, SIZE, DURATION: We evaluated the antagonistic effects of MenSCs on myofibroblast differentiation as well as the broader effect of the Hippo/TAZ signaling pathway on TGFβ-mediated induction of myofibroblast gene expression. The study design was based on a cohort of clinical proliferative phase endometrial samples obtained from three healthy premenopausal females with regular menstrual cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: ESCs were cocultured with MenSCs or in MenSC-conditioned medium. Fibrotic markers (αSMA, collagen I, CTGF and fibronectin) as well as proliferation and wound-healing abilities were evaluated. Components of the Hippo/TAZ pathway (TAZ, p-TAZ, MOB1, p-MOB1, LATS1 and p-LATS1) were also investigated. Cell Counting Kit 8, wound healing assay, real-time PCR, western blotting, immunofluorescence and ...