HMGA2-induced epithelial–mesenchymal transition is reversed by let-7d in intrauterine adhesions

Song, Minmin; Cao, Chenrui; Zhou, Zhenhua; Yao, Simin; Jiang, Pengju; Wang, Huiyan; Zhao, Guangfeng; Hu, Yali

doi:10.1093/molehr/gaaa074

Cited by 11 publications

(6 citation statements)

References 33 publications

(17 reference statements)

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“…Furthermore, numerous studies have indicated that transforming growth factor (TGF)-β is a cytokine that participates in regulating diverse biological functions, including cell proliferation, apoptosis, and differentiation [ 11 , 12 ]. Importantly, previous studies have reported that TGF-β can induce endometrial fibrosis [ 13 , 14 ] and TGF-β treated ESC can serve as the in vitro model of IUA [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

MiR-543 Inhibits the Migration and Epithelial-To-Mesenchymal Transition of TGF-β-Treated Endometrial Stromal Cells via the MAPK and Wnt/β-Catenin Signaling Pathways

Wang

Liu

Wei

et al. 2021

Pathol. Oncol. Res.

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Intrauterine adhesion (IUA) is one of the most prevalent reproductive system diseases in females. MicroRNAs (miRNAs) are reported to be master regulators in a variety of diseases, including IUA, but the role of microRNA-543 (miR-543) in IUA remains to be elucidated. In this study, we observed that miR-543 was downregulated in transforming growth factor-beta (TGF-β)-treated endometrial stromal cells (ESCs). Functionally, we observed that miR-543 suppressed the migration, epithelial-to-mesenchymal transition (EMT), and inhibited expression of extracellular matrix (ECM) proteins in TGF-β-treated ESCs. Mechanistically, MAPK1 is targeted by miR-543 after prediction and screening. A luciferase reporter assay demonstrated that miR-543 complementarily binds with the 3′ untranslated region of mitogen-activated protein kinase 1 (MAPK1), and western blot analysis indicated that miR-543 negatively regulates MAPK1 protein levels. In addition, results from rescue assays showed that miR-543 inhibits the migration and EMT of TGF-β-treated ESCs by targeting MAPK1. In addition, we observed that miR-543 inactivates the Wnt/β-catenin signaling pathway through inhibiting the phosphorylation of MAPK1 and β-catenin. Finally, we confirmed that miR-543 represses migration, EMT and inhibits levels of ECM proteins in TGF-β-treated ESCs by targeting the Wnt/β-catenin signaling pathway. Our results demonstrated that miR-543 suppresses migration and EMT of TGF-β-treated ESCs by targeting the MAPK and Wnt/β-catenin pathways.

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Section: Introductionmentioning

confidence: 99%

MiR-543 Inhibits the Migration and Epithelial-To-Mesenchymal Transition of TGF-β-Treated Endometrial Stromal Cells via the MAPK and Wnt/β-Catenin Signaling Pathways

Wang

Liu

Wei

et al. 2021

Pathol. Oncol. Res.

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“…Although the incidence of IUA increases each year, effective treatment options to reduce the incidence of re-adhesion and promote fertility remain lacking [9]. Potentially, activated fibroblasts may be derived from resting fibroblasts in the tissue, via epithelial-to-mesenchymal transformation, or from the bone marrow [25], [35,36]. In this study, we demonstrate for the first time that endothelial cells also promote the emergence of Further studies are needed in this area.…”

Section: Discussionmentioning

confidence: 70%

EndMT: New findings on the origin of myofibroblasts in endometrial fibrosis of intrauterine adhesions

Bao

Fan

et al. 2022

Reprod Biol Endocrinol

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Background Intrauterine adhesion (IUA) is one of the leading causes of infertility and the main clinical challenge is the high recurrence rate. The key to solving this dilemma lies in elucidating the mechanisms of endometrial fibrosis. The aim of our team is to study the mechanism underlying intrauterine adhesion fibrosis and the origin of fibroblasts in the repair of endometrial fibrosis. Methods Our experimental study involving an animal model of intrauterine adhesion and detection of fibrosis-related molecules. The levels of molecular factors related to the endothelial-to-mesenchymal transition (EndMT) were examined in a rat model of intrauterine adhesion using immunofluorescence, immunohistochemistry, qPCR and Western blot analyses. Main outcome measures are levels of the endothelial marker CD31 and the mesenchymal markers alpha-smooth muscle actin (α-SMA) and vimentin. Results Immunofluorescence co-localization of CD31 and a-SMA showed that 14 days after moulding, double positive cells for CD31 and a-SMA could be clearly observed in the endometrium. Decreased CD31 levels and increased α-SMA and vimentin levels indicate that EndMT is involved in intrauterine adhesion fibrosis. Conclusions Endothelial cells promote the emergence of fibroblasts via the EndMT during the endometrial fibrosis of intrauterine adhesions.

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“…High mobility group AT-hook 2 (HMGA2) was regarded as an important regulator in EMT processes in some fibrotic diseases, such as pulmonary fibrosis, lens fibrosis and renal fibrosis. Similarly, in IUA patients and animal models, Song et al ( 21 ) also observed the overexpression of HMGA2 directly mediated EMT. They further found that HMGA2 expression can be directly inhabited by let-7d to protect EEC from EMT.…”

Section: The Formation Of Iuamentioning

confidence: 83%

Extracellular Vesicles Derived from Mesenchymal Stem Cells as Cell-Free Therapy for Intrauterine Adhesion

2023

Int J Stem Cells

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Intrauterine adhesion (IUA) can occur after trauma to the basal layer of the endometrium, contributing to severe complications in females, such as infertility and amenorrhea. To date, the proposed therapeutic strategies are targeted to relieve IUA, such as hysteroscopic adhesiolysis, Foley catheter balloon, and hyaluronic acid injection have been applied in the clinic. However, these approaches showed limited effects in alleviating endometrial fibrosis and thin endometrium. Mesenchymal stem cells (MSCs) can offer the potential for endometrium regeneration owing to reduce inflammation and release growth factors. On this basis, MSCs have been proposed as promising methods to treat intrauterine adhesion. However, due to the drawbacks of cell therapy, the possible therapeutic use of extracellular vesicles released by stem cells is raising increasing interest. The paracrine effect, mediated by MSCs derived extracellular vehicles (MSC-EVs), has recently been suggested as a mechanism for their therapeutic properties. Here, we summarizes the main pathological mechanisms involved in intrauterine adhesion, the biogenesis and characteristics of extracellular vesicles, explaining how these vesicles could provide new opportunities for MSCs.

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HMGA2-induced epithelial–mesenchymal transition is reversed by let-7d in intrauterine adhesions

Cited by 11 publications

References 33 publications

MiR-543 Inhibits the Migration and Epithelial-To-Mesenchymal Transition of TGF-β-Treated Endometrial Stromal Cells via the MAPK and Wnt/β-Catenin Signaling Pathways

MiR-543 Inhibits the Migration and Epithelial-To-Mesenchymal Transition of TGF-β-Treated Endometrial Stromal Cells via the MAPK and Wnt/β-Catenin Signaling Pathways

EndMT: New findings on the origin of myofibroblasts in endometrial fibrosis of intrauterine adhesions

Extracellular Vesicles Derived from Mesenchymal Stem Cells as Cell-Free Therapy for Intrauterine Adhesion

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