Cargando…
The Expression of TGF-β1, SMAD3, ILK and miRNA-21 in the Ectopic and Eutopic Endometrium of Women with Endometriosis
The molecular pathogenesis of endometriosis has been associated with pathological alterations of protein expression via disturbances in homeostatic genes, miRNA expression profiles, and signaling pathways that play an essential role in the epithelial-mesenchymal transition (EMT) process. TGF-β1 has...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917033/ https://www.ncbi.nlm.nih.gov/pubmed/36768775 http://dx.doi.org/10.3390/ijms24032453 |
_version_ | 1784886271781371904 |
---|---|
author | Zubrzycka, Anna Migdalska-Sęk, Monika Jędrzejczyk, Sławomir Brzeziańska-Lasota, Ewa |
author_facet | Zubrzycka, Anna Migdalska-Sęk, Monika Jędrzejczyk, Sławomir Brzeziańska-Lasota, Ewa |
author_sort | Zubrzycka, Anna |
collection | PubMed |
description | The molecular pathogenesis of endometriosis has been associated with pathological alterations of protein expression via disturbances in homeostatic genes, miRNA expression profiles, and signaling pathways that play an essential role in the epithelial-mesenchymal transition (EMT) process. TGF-β1 has been hypothesized to play a key role in the development and progression of endometriosis, but the activation of a specific mechanism via the TGF-β-SMAD-ILK axis in the formation of endometriotic lesions is poorly understood. The aim of this study was to assess the expression of EMT markers (TGF-β1, SMAD3, ILK) and miR-21 in ectopic endometrium (ECE), in its eutopic (EUE) counterpart, and in the endometrium of healthy women. The expression level of the tested genes and miRNA was also evaluated in peripheral blood mononuclear cells (PBMC) in women with and without endometriosis. Fifty-four patients (n = 54; with endometriosis, n = 29, and without endometriosis, n = 25) were enrolled in the study. The expression levels (RQ) of the studied genes and miRNA were evaluated using qPCR. Endometriosis patients manifested higher TGF-β1, SMAD3, and ILK expression levels in the eutopic endometrium and a decreased expression level in the ectopic lesions in relation to control tissue. Compared to the endometrium of healthy participants, miR-21 expression levels did not change in the eutopic endometrium of women with endometriosis, but the RQ was higher in their endometrial implants. In PBMC, negative correlations were found between the expression level of miR-21 and the studied genes, with the strongest statistically significant correlation observed between miR-21 and TGF-β1. Our results suggest the loss of the endometrial epithelial phenotype defined by the differential expression of the TGF-β1, SMAD3 and ILK genes in the eutopic and ectopic endometrium. We concluded that the TGF-β1-SMAD3-ILK signaling pathway, probably via a mechanism related to the EMT, may be important in the pathogenesis of endometriosis. We also identified miR-21 as a possible inhibitor of this TGF-β1-SMAD3-ILK axis. |
format | Online Article Text |
id | pubmed-9917033 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99170332023-02-11 The Expression of TGF-β1, SMAD3, ILK and miRNA-21 in the Ectopic and Eutopic Endometrium of Women with Endometriosis Zubrzycka, Anna Migdalska-Sęk, Monika Jędrzejczyk, Sławomir Brzeziańska-Lasota, Ewa Int J Mol Sci Article The molecular pathogenesis of endometriosis has been associated with pathological alterations of protein expression via disturbances in homeostatic genes, miRNA expression profiles, and signaling pathways that play an essential role in the epithelial-mesenchymal transition (EMT) process. TGF-β1 has been hypothesized to play a key role in the development and progression of endometriosis, but the activation of a specific mechanism via the TGF-β-SMAD-ILK axis in the formation of endometriotic lesions is poorly understood. The aim of this study was to assess the expression of EMT markers (TGF-β1, SMAD3, ILK) and miR-21 in ectopic endometrium (ECE), in its eutopic (EUE) counterpart, and in the endometrium of healthy women. The expression level of the tested genes and miRNA was also evaluated in peripheral blood mononuclear cells (PBMC) in women with and without endometriosis. Fifty-four patients (n = 54; with endometriosis, n = 29, and without endometriosis, n = 25) were enrolled in the study. The expression levels (RQ) of the studied genes and miRNA were evaluated using qPCR. Endometriosis patients manifested higher TGF-β1, SMAD3, and ILK expression levels in the eutopic endometrium and a decreased expression level in the ectopic lesions in relation to control tissue. Compared to the endometrium of healthy participants, miR-21 expression levels did not change in the eutopic endometrium of women with endometriosis, but the RQ was higher in their endometrial implants. In PBMC, negative correlations were found between the expression level of miR-21 and the studied genes, with the strongest statistically significant correlation observed between miR-21 and TGF-β1. Our results suggest the loss of the endometrial epithelial phenotype defined by the differential expression of the TGF-β1, SMAD3 and ILK genes in the eutopic and ectopic endometrium. We concluded that the TGF-β1-SMAD3-ILK signaling pathway, probably via a mechanism related to the EMT, may be important in the pathogenesis of endometriosis. We also identified miR-21 as a possible inhibitor of this TGF-β1-SMAD3-ILK axis. MDPI 2023-01-26 /pmc/articles/PMC9917033/ /pubmed/36768775 http://dx.doi.org/10.3390/ijms24032453 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zubrzycka, Anna Migdalska-Sęk, Monika Jędrzejczyk, Sławomir Brzeziańska-Lasota, Ewa The Expression of TGF-β1, SMAD3, ILK and miRNA-21 in the Ectopic and Eutopic Endometrium of Women with Endometriosis |
title | The Expression of TGF-β1, SMAD3, ILK and miRNA-21 in the Ectopic and Eutopic Endometrium of Women with Endometriosis |
title_full | The Expression of TGF-β1, SMAD3, ILK and miRNA-21 in the Ectopic and Eutopic Endometrium of Women with Endometriosis |
title_fullStr | The Expression of TGF-β1, SMAD3, ILK and miRNA-21 in the Ectopic and Eutopic Endometrium of Women with Endometriosis |
title_full_unstemmed | The Expression of TGF-β1, SMAD3, ILK and miRNA-21 in the Ectopic and Eutopic Endometrium of Women with Endometriosis |
title_short | The Expression of TGF-β1, SMAD3, ILK and miRNA-21 in the Ectopic and Eutopic Endometrium of Women with Endometriosis |
title_sort | expression of tgf-β1, smad3, ilk and mirna-21 in the ectopic and eutopic endometrium of women with endometriosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917033/ https://www.ncbi.nlm.nih.gov/pubmed/36768775 http://dx.doi.org/10.3390/ijms24032453 |
work_keys_str_mv | AT zubrzyckaanna theexpressionoftgfb1smad3ilkandmirna21intheectopicandeutopicendometriumofwomenwithendometriosis AT migdalskasekmonika theexpressionoftgfb1smad3ilkandmirna21intheectopicandeutopicendometriumofwomenwithendometriosis AT jedrzejczyksławomir theexpressionoftgfb1smad3ilkandmirna21intheectopicandeutopicendometriumofwomenwithendometriosis AT brzezianskalasotaewa theexpressionoftgfb1smad3ilkandmirna21intheectopicandeutopicendometriumofwomenwithendometriosis AT zubrzyckaanna expressionoftgfb1smad3ilkandmirna21intheectopicandeutopicendometriumofwomenwithendometriosis AT migdalskasekmonika expressionoftgfb1smad3ilkandmirna21intheectopicandeutopicendometriumofwomenwithendometriosis AT jedrzejczyksławomir expressionoftgfb1smad3ilkandmirna21intheectopicandeutopicendometriumofwomenwithendometriosis AT brzezianskalasotaewa expressionoftgfb1smad3ilkandmirna21intheectopicandeutopicendometriumofwomenwithendometriosis |