Overactivated Sonic Hedgehog Signaling Aggravates Intrauterine Adhesion by Inhibiting Autophagy in Endometrial Stromal Cells

    September 2020 in “ Cell Death and Disease ”
    Wei Cheng, Yibin Pan, Yinli Zhang, Yongdong Dai, Lingling Jiang, Libing Shi, Weijie Yang, Shiqian Xu, Yingyi Zhang, Wenzhi Xu, Yanling Zhang, Xiaona Lin, Songying Zhang
    TLDR Overactive sonic hedgehog signaling worsens uterine scarring by reducing cell recycling.
    The study investigated the role of autophagy in sonic hedgehog (SHH) signaling-induced endometrial fibrosis, which contributes to intrauterine adhesion (IUA) and infertility. It was found that impaired autophagy was involved in the SHH pathway's exacerbation of endometrial fibrosis. In both human endometrial stromal cells and a mouse model, the SHH pathway negatively regulated autophagy through the pAKT-mTORC1 pathway. Modulating autophagy, either by promoting it with rapamycin or inhibiting it with chloroquine, influenced the extent of fibrosis. These findings suggested that targeting autophagy could be a novel approach for treating IUA.
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