Uvaol attenuates TGF-β1-induced epithelial-mesenchymal transition in human alveolar epithelial cells by modulating expression and membrane localization of β-catenin
The epithelial-mesenchymal transition (EMT) is a biological process in which epithelial cells change into mesenchymal cells with fibroblast-like characteristics. EMT plays a crucial role in the progression of fibrosis. Classical inducers associated with the maintenance of EMT, such as TGF-β1, have b...
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Frontiers Media S.A.
2025-01-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1504556/full |
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| author | Liliane Patrícia Gonçalves Tenório Liliane Patrícia Gonçalves Tenório Liliane Patrícia Gonçalves Tenório Liliane Patrícia Gonçalves Tenório Liliane Patrícia Gonçalves Tenório Felipe Henrique da Cunha Xavier Felipe Henrique da Cunha Xavier Felipe Henrique da Cunha Xavier Felipe Henrique da Cunha Xavier Mônica Silveira Wagner Kayo Moreira Bagri Erick Gabriel Alves Ferreira Romulo Galvani Romulo Galvani Romulo Galvani Romulo Galvani Claudia Mermelstein Adriana Cesar Bonomo Adriana Cesar Bonomo Adriana Cesar Bonomo Adriana Cesar Bonomo Wilson Savino Wilson Savino Wilson Savino Wilson Savino Emiliano Barreto Emiliano Barreto |
| author_facet | Liliane Patrícia Gonçalves Tenório Liliane Patrícia Gonçalves Tenório Liliane Patrícia Gonçalves Tenório Liliane Patrícia Gonçalves Tenório Liliane Patrícia Gonçalves Tenório Felipe Henrique da Cunha Xavier Felipe Henrique da Cunha Xavier Felipe Henrique da Cunha Xavier Felipe Henrique da Cunha Xavier Mônica Silveira Wagner Kayo Moreira Bagri Erick Gabriel Alves Ferreira Romulo Galvani Romulo Galvani Romulo Galvani Romulo Galvani Claudia Mermelstein Adriana Cesar Bonomo Adriana Cesar Bonomo Adriana Cesar Bonomo Adriana Cesar Bonomo Wilson Savino Wilson Savino Wilson Savino Wilson Savino Emiliano Barreto Emiliano Barreto |
| author_sort | Liliane Patrícia Gonçalves Tenório |
| collection | DOAJ |
| description | The epithelial-mesenchymal transition (EMT) is a biological process in which epithelial cells change into mesenchymal cells with fibroblast-like characteristics. EMT plays a crucial role in the progression of fibrosis. Classical inducers associated with the maintenance of EMT, such as TGF-β1, have become targets of several anti-EMT therapeutic strategies. Natural products from the pentacyclic triterpene class have emerged as promising elements in inhibiting EMT. Uvaol is a pentacyclic triterpene found in olive trees (Olea europaea L.) known for its anti-inflammatory, antioxidant, and antiproliferative properties. Yet, its effect on the TGF-β1-induced EMT in alveolar epithelial cells is unknown. The present study aimed to investigate the impact of uvaol upon TGF-β1-induced EMT in a cultured A549 human alveolar epithelial cell line, a classic in vitro model for studies of EMT. Changes in cell shape were measured using phase-contrast and confocal microscopy, whereas protein expression levels were measured using immunofluorescence, flow cytometry, and Western blotting. We also performed wound scratch experiments to explore its effects on cell migration. Uvaol had no significant cytotoxic effects on A549 cells. By contrast, the changes in the cell morphology consistent with TGF-β1-induced EMT were largely suppressed by treatment with uvaol. In addition, increased contents of mesenchymal markers, namely, vimentin, N-cadherin, and fibronectin in TGF-β1-induced A549 cells, were downregulated by uvaol treatment. Furthermore, the TGF-β1-induced migration of A549 cells was significantly suppressed by uvaol. Mechanistically, uvaol prevented the nuclear translocation of β-catenin and reduced the TGF-β1-induced levels of ZEB1 in A549 cells. These results provide compelling evidence that uvaol inhibits EMT by regulating proteins related to the mesenchymal profile in human alveolar epithelial cells, likely by modulating β-catenin and ZEB1 levels. |
| format | Article |
| id | doaj-art-983e211bc9c84b3ebf02b7a8fda2d99c |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-983e211bc9c84b3ebf02b7a8fda2d99c2025-01-07T06:44:19ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.15045561504556Uvaol attenuates TGF-β1-induced epithelial-mesenchymal transition in human alveolar epithelial cells by modulating expression and membrane localization of β-cateninLiliane Patrícia Gonçalves Tenório0Liliane Patrícia Gonçalves Tenório1Liliane Patrícia Gonçalves Tenório2Liliane Patrícia Gonçalves Tenório3Liliane Patrícia Gonçalves Tenório4Felipe Henrique da Cunha Xavier5Felipe Henrique da Cunha Xavier6Felipe Henrique da Cunha Xavier7Felipe Henrique da Cunha Xavier8Mônica Silveira Wagner9Kayo Moreira Bagri10Erick Gabriel Alves Ferreira11Romulo Galvani12Romulo Galvani13Romulo Galvani14Romulo Galvani15Claudia Mermelstein16Adriana Cesar Bonomo17Adriana Cesar Bonomo18Adriana Cesar Bonomo19Adriana Cesar Bonomo20Wilson Savino21Wilson Savino22Wilson Savino23Wilson Savino24Emiliano Barreto25Emiliano Barreto26Cell Biology Laboratory, Federal University of Alagoas, Maceió, BrazilLaboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilNational Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilRio de Janeiro Network on Neuroinflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilINOVA-IOC Network on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLaboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilNational Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilRio de Janeiro Network on Neuroinflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilINOVA-IOC Network on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilCell Structure and Dynamics Laboratory, National Cancer Institute, Rio de Janeiro, BrazilMuscle Differentiation Laboratory, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilCell Biology Laboratory, Federal University of Alagoas, Maceió, BrazilLaboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilNational Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilRio de Janeiro Network on Neuroinflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilINOVA-IOC Network on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilMuscle Differentiation Laboratory, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilLaboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilNational Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilRio de Janeiro Network on Neuroinflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilINOVA-IOC Network on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLaboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilNational Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilRio de Janeiro Network on Neuroinflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilINOVA-IOC Network on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilCell Biology Laboratory, Federal University of Alagoas, Maceió, BrazilNational Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilThe epithelial-mesenchymal transition (EMT) is a biological process in which epithelial cells change into mesenchymal cells with fibroblast-like characteristics. EMT plays a crucial role in the progression of fibrosis. Classical inducers associated with the maintenance of EMT, such as TGF-β1, have become targets of several anti-EMT therapeutic strategies. Natural products from the pentacyclic triterpene class have emerged as promising elements in inhibiting EMT. Uvaol is a pentacyclic triterpene found in olive trees (Olea europaea L.) known for its anti-inflammatory, antioxidant, and antiproliferative properties. Yet, its effect on the TGF-β1-induced EMT in alveolar epithelial cells is unknown. The present study aimed to investigate the impact of uvaol upon TGF-β1-induced EMT in a cultured A549 human alveolar epithelial cell line, a classic in vitro model for studies of EMT. Changes in cell shape were measured using phase-contrast and confocal microscopy, whereas protein expression levels were measured using immunofluorescence, flow cytometry, and Western blotting. We also performed wound scratch experiments to explore its effects on cell migration. Uvaol had no significant cytotoxic effects on A549 cells. By contrast, the changes in the cell morphology consistent with TGF-β1-induced EMT were largely suppressed by treatment with uvaol. In addition, increased contents of mesenchymal markers, namely, vimentin, N-cadherin, and fibronectin in TGF-β1-induced A549 cells, were downregulated by uvaol treatment. Furthermore, the TGF-β1-induced migration of A549 cells was significantly suppressed by uvaol. Mechanistically, uvaol prevented the nuclear translocation of β-catenin and reduced the TGF-β1-induced levels of ZEB1 in A549 cells. These results provide compelling evidence that uvaol inhibits EMT by regulating proteins related to the mesenchymal profile in human alveolar epithelial cells, likely by modulating β-catenin and ZEB1 levels.https://www.frontiersin.org/articles/10.3389/fphar.2024.1504556/fulluvaolTGF-β1epithelial-mesenchymal transitionβ-catenincell migration |
| spellingShingle | Liliane Patrícia Gonçalves Tenório Liliane Patrícia Gonçalves Tenório Liliane Patrícia Gonçalves Tenório Liliane Patrícia Gonçalves Tenório Liliane Patrícia Gonçalves Tenório Felipe Henrique da Cunha Xavier Felipe Henrique da Cunha Xavier Felipe Henrique da Cunha Xavier Felipe Henrique da Cunha Xavier Mônica Silveira Wagner Kayo Moreira Bagri Erick Gabriel Alves Ferreira Romulo Galvani Romulo Galvani Romulo Galvani Romulo Galvani Claudia Mermelstein Adriana Cesar Bonomo Adriana Cesar Bonomo Adriana Cesar Bonomo Adriana Cesar Bonomo Wilson Savino Wilson Savino Wilson Savino Wilson Savino Emiliano Barreto Emiliano Barreto Uvaol attenuates TGF-β1-induced epithelial-mesenchymal transition in human alveolar epithelial cells by modulating expression and membrane localization of β-catenin Frontiers in Pharmacology uvaol TGF-β1 epithelial-mesenchymal transition β-catenin cell migration |
| title | Uvaol attenuates TGF-β1-induced epithelial-mesenchymal transition in human alveolar epithelial cells by modulating expression and membrane localization of β-catenin |
| title_full | Uvaol attenuates TGF-β1-induced epithelial-mesenchymal transition in human alveolar epithelial cells by modulating expression and membrane localization of β-catenin |
| title_fullStr | Uvaol attenuates TGF-β1-induced epithelial-mesenchymal transition in human alveolar epithelial cells by modulating expression and membrane localization of β-catenin |
| title_full_unstemmed | Uvaol attenuates TGF-β1-induced epithelial-mesenchymal transition in human alveolar epithelial cells by modulating expression and membrane localization of β-catenin |
| title_short | Uvaol attenuates TGF-β1-induced epithelial-mesenchymal transition in human alveolar epithelial cells by modulating expression and membrane localization of β-catenin |
| title_sort | uvaol attenuates tgf β1 induced epithelial mesenchymal transition in human alveolar epithelial cells by modulating expression and membrane localization of β catenin |
| topic | uvaol TGF-β1 epithelial-mesenchymal transition β-catenin cell migration |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1504556/full |
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