Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China.
Chin Med J (Engl). 2017 Nov 20;130(22):2732-2737. doi: 10.4103/0366-6999.218013.
Intrauterine adhesion (IUA) is a major health problem that causes infertility, menstrual irregularities, and recurrent pregnancy losses in women. Unfortunately, treatments for IUA are limited, and there are currently no effective strategies for preventing IUA recurrence. In this review, we introduced the role of Hippo signaling in the normal endometrium and IUA and described the mechanisms by which the Hippo pathway integrates with the Wnt and transforming growth factor-β (TGF-β) signaling pathways to form an intricate network governing the development of fibrosis.
Original research articles in English that were published until July 2017 were collected from the PubMed database.
Literature search was conducted using the search terms "endometrial fibrosis OR fibrosis AND or OR intrauterine adhesion OR Asherman syndrome OR IUA," "Hippo AND or OR Hippo/TAZ," "TGF-β," and "Wnt." Related original research articles were included in the comprehensive analysis.
Endometrial fibrosis is recognized as a key pathological event in the development of IUA, which is characterized by epithelial/fibroblast-myofibroblast transition. Myofibroblasts play crucial roles in the pathogenesis of fibrous scarring, and myofibroblast differentiation can be triggered by multiple signaling pathways. Hippo signaling is a critical regulator of the epithelial/fibroblast-myofibroblast transition and α-smooth muscle actin, which exhibits a specific spatiotemporal expression in the endometrium.
Hippo signaling plays a critical role in fibrous diseases and participates in cross talks with Wnt and TGF-β signaling. Our findings not only contributed to knowledge on the pathogenesis of endometrial fibrosis, but can also serve as a useful resource for developing specific molecular inhibitors for IUA treatment and prevention.
宫腔粘连（IUA）是导致女性不孕、月经不规律和反复妊娠丢失的主要健康问题。不幸的是，IUA 的治疗方法有限，目前尚无预防 IUA 复发的有效策略。在本综述中，我们介绍了 Hippo 信号通路在正常子宫内膜和 IUA 中的作用，并描述了 Hippo 通路如何与 Wnt 和转化生长因子-β（TGF-β）信号通路整合，形成一个复杂的网络，调节纤维化的发生。
从 PubMed 数据库中收集了截至 2017 年 7 月发表的英文原始研究文章。
使用“子宫内膜纤维化 OR 纤维化 AND 或 OR 宫腔粘连 OR Asherman 综合征 OR IUA”、“Hippo AND 或 OR Hippo/TAZ”、“TGF-β”和“Wnt”等搜索词进行文献检索。纳入了相关的原始研究文章进行综合分析。
子宫内膜纤维化被认为是 IUA 发展的关键病理事件，其特征是上皮/成纤维细胞-肌成纤维细胞转化。肌成纤维细胞在纤维性瘢痕形成的发病机制中起着关键作用，并且可以通过多种信号通路触发肌成纤维细胞分化。Hippo 信号通路是上皮/成纤维细胞-肌成纤维细胞转化和α-平滑肌肌动蛋白的关键调节剂，在子宫内膜中表现出特定的时空表达。
Hippo 信号通路在纤维性疾病中发挥着关键作用，并与 Wnt 和 TGF-β信号通路相互作用。我们的研究结果不仅有助于了解子宫内膜纤维化的发病机制，还可以为开发用于治疗和预防 IUA 的特异性分子抑制剂提供有用的资源。
