ΔNp63α-induced DUSP4/GSK3β/SNAI1 pathway in epithelial cells drives endometrial fibrosis.

Cell Death & Disease
Guangfeng ZhaoYali Hu

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 targ...Continue Reading

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Citations

Jul 3, 2021·Pathology, Research and Practice·Tao WangJian Yin
Sep 30, 2021·Science China. Life Sciences·Xiwen ZhangYali Hu
Jan 9, 2022·Reproductive Biology and Endocrinology : RB&E·Chengcheng XuWei Xia

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Methods Mentioned

BETA
RNA-seq
PCR
biopsy
biopsies
confocal microscopy
transfection
flow cytometry

Software Mentioned

GraphPad Prism
pheatmap
R
Hisat2
house Perl scripts
in
TermFinder
Cuffdiff
Perl

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