Transient and Prolonged Activation of Wnt Signaling Contribute Oppositely to the Pathogenesis of Asherman’s Syndrome

Asherman’s Syndrome (AS) is caused by dysfunction of endometrial regenerative ability, which is controlled by adult stem cells and their niche. The Wnt signaling pathway has been demonstrated to be implicated in this process. This study aimed to clarify the relationship between the Wnt signaling pat...

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Main Authors: Xiang Xue, Xiaoli Li, Jinmeng Yao, Xue Zhang, Xu Ren, Shan Xu
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/15/8808
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author Xiang Xue
Xiaoli Li
Jinmeng Yao
Xue Zhang
Xu Ren
Shan Xu
author_facet Xiang Xue
Xiaoli Li
Jinmeng Yao
Xue Zhang
Xu Ren
Shan Xu
author_sort Xiang Xue
collection DOAJ
description Asherman’s Syndrome (AS) is caused by dysfunction of endometrial regenerative ability, which is controlled by adult stem cells and their niche. The Wnt signaling pathway has been demonstrated to be implicated in this process. This study aimed to clarify the relationship between the Wnt signaling pathway and the progression of AS after initial endometrial damage. Endometria with and without adhesion as well as from the intrauterine devices three months after the surgery were collected to compare the area of fibrosis. The area% of fibrosis did not vary significantly. Significantly higher expression of non-phosphorylated β-catenin, Wnt5a and Wnt7a was identified in the endometria with adhesion. The CD140b<sup>+</sup>CD146<sup>+</sup> endometrial stem-like cells were present in the endometria with adhesion. Both Wnt5a and Wnt7a promoted stem cell proliferation. However, only Wnt7a preserved stem cell population by stimulating self-renewal. A rat endometrial injury model was established to investigate the effect of the activated Wnt/β-catenin signaling pathway on endometrial healing. We found that a transient activation of the Wnt/β-catenin signaling pathway promoted angiogenesis and increased the number of glands. In conclusion, transient activation of the Wnt/β-catenin signaling pathway during the acute endometrial damage may help the tissue regeneration, while prolonged activation may correlate to fibrosis formation.
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spelling doaj.art-fb4b051fdae64b5d9a63da547afd3dc12023-11-30T22:31:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012315880810.3390/ijms23158808Transient and Prolonged Activation of Wnt Signaling Contribute Oppositely to the Pathogenesis of Asherman’s SyndromeXiang Xue0Xiaoli Li1Jinmeng Yao2Xue Zhang3Xu Ren4Shan Xu5Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, ChinaDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, ChinaDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, ChinaCore Research Laboratory, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, ChinaDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, ChinaAsherman’s Syndrome (AS) is caused by dysfunction of endometrial regenerative ability, which is controlled by adult stem cells and their niche. The Wnt signaling pathway has been demonstrated to be implicated in this process. This study aimed to clarify the relationship between the Wnt signaling pathway and the progression of AS after initial endometrial damage. Endometria with and without adhesion as well as from the intrauterine devices three months after the surgery were collected to compare the area of fibrosis. The area% of fibrosis did not vary significantly. Significantly higher expression of non-phosphorylated β-catenin, Wnt5a and Wnt7a was identified in the endometria with adhesion. The CD140b<sup>+</sup>CD146<sup>+</sup> endometrial stem-like cells were present in the endometria with adhesion. Both Wnt5a and Wnt7a promoted stem cell proliferation. However, only Wnt7a preserved stem cell population by stimulating self-renewal. A rat endometrial injury model was established to investigate the effect of the activated Wnt/β-catenin signaling pathway on endometrial healing. We found that a transient activation of the Wnt/β-catenin signaling pathway promoted angiogenesis and increased the number of glands. In conclusion, transient activation of the Wnt/β-catenin signaling pathway during the acute endometrial damage may help the tissue regeneration, while prolonged activation may correlate to fibrosis formation.https://www.mdpi.com/1422-0067/23/15/8808Asherman’s SyndromeWnt signaling pathwayendometriumstem cells
spellingShingle Xiang Xue
Xiaoli Li
Jinmeng Yao
Xue Zhang
Xu Ren
Shan Xu
Transient and Prolonged Activation of Wnt Signaling Contribute Oppositely to the Pathogenesis of Asherman’s Syndrome
International Journal of Molecular Sciences
Asherman’s Syndrome
Wnt signaling pathway
endometrium
stem cells
title Transient and Prolonged Activation of Wnt Signaling Contribute Oppositely to the Pathogenesis of Asherman’s Syndrome
title_full Transient and Prolonged Activation of Wnt Signaling Contribute Oppositely to the Pathogenesis of Asherman’s Syndrome
title_fullStr Transient and Prolonged Activation of Wnt Signaling Contribute Oppositely to the Pathogenesis of Asherman’s Syndrome
title_full_unstemmed Transient and Prolonged Activation of Wnt Signaling Contribute Oppositely to the Pathogenesis of Asherman’s Syndrome
title_short Transient and Prolonged Activation of Wnt Signaling Contribute Oppositely to the Pathogenesis of Asherman’s Syndrome
title_sort transient and prolonged activation of wnt signaling contribute oppositely to the pathogenesis of asherman s syndrome
topic Asherman’s Syndrome
Wnt signaling pathway
endometrium
stem cells
url https://www.mdpi.com/1422-0067/23/15/8808
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