1. ΔNp63α-induced DUSP4/GSK3β/SNAI1 pathway in epithelial cells drives endometrial fibrosis
- Author
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Zhenhua Zhou, Limin Wang, Hui Zhu, Haining Lv, Dan Liu, Chenyan Dai, Qianwen Wu, Yan Zhou, Ruotian Li, Peipei Jiang, Jianwu Dai, Simin Yao, Yali Hu, Yun Cao, Minmin Song, Guangfeng Zhao, and Huiyan Wang
- Subjects
Cancer Research ,Molecular biology ,Reproductive disorders ,Oncology and Carcinogenesis ,Immunology ,Context (language use) ,Article ,Transcriptome ,Endometrium ,Mice ,Cellular and Molecular Neuroscience ,Uterine Cancer ,Fibrosis ,In vivo ,medicine ,Animals ,Humans ,2.1 Biological and endogenous factors ,lcsh:QH573-671 ,Aetiology ,Cancer ,Glycogen Synthase Kinase 3 beta ,lcsh:Cytology ,business.industry ,Epithelial Cells ,Cell Biology ,medicine.disease ,Phenotype ,SNAI1 ,Cancer research ,Female ,Ectopic expression ,Biochemistry and Cell Biology ,Signal transduction ,business ,Signal Transduction - Abstract
Epithelial homeostasis plays an essential role in maintaining endometrial function. But the epithelial role in endometrial fibrosis has been less studied. Previously, we showed that ectopic expression of ΔNp63α is associated with fibrosis process and epithelial dysfunction in endometria of patients with intrauterine adhesions (IUAs). Since ΔNp63α is profoundly involved in maintaining the epithelial homeostasis, we hereby focused on its roles in regulating the function and phenotype of endometrial epithelial cells (EECs) in context of endometrial fibrosis. We identified a typical type 2 epithelial-to-mesenchymal transition (EMT) in EECs from IUA patients and this process was induced by the forced expression of ΔNp63α in EECs. In transcriptomic analysis, we found that diverse signaling pathways regulated by ΔNp63α were involved in pro-EMT. We demonstrated that the DUSP4/GSK-3β/SNAI1 pathway was critical in transducing the pro-EMT signals initiated by ΔNp63α, while bFGF reversed ΔNp63α-induced EMT and endometrial fibrosis both in vitro and in vivo by blocking DUSP4/GSK3β/SNAI1 pathway. Taken together, our findings are important to understand the molecular mechanisms of endometrial fibrosis and to provide potential therapeutic targets.
- Published
- 2020