5-Aza-2′-Deoxycytidine (5-Aza-dC, Decitabine) Inhibits Collagen Type I and III Expression in TGF-β1-Treated Equine Endometrial Fibroblasts
Endometrosis negatively affects endometrial function and fertility in mares, due to excessive deposition of type I (COL1) and type III (COL3) collagens. The pro-fibrotic transforming growth factor (TGF-β1) induces myofibroblast differentiation, characterized by α-smooth muscle actin (α-SMA) expressi...
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MDPI AG
2023-03-01
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| Series: | Animals |
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| Online Access: | https://www.mdpi.com/2076-2615/13/7/1212 |
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| author | Joana Alpoim-Moreira Anna Szóstek-Mioduchowska Magda Słyszewska Maria Rosa Rebordão Dariusz J. Skarzynski Graça Ferreira-Dias |
| author_facet | Joana Alpoim-Moreira Anna Szóstek-Mioduchowska Magda Słyszewska Maria Rosa Rebordão Dariusz J. Skarzynski Graça Ferreira-Dias |
| author_sort | Joana Alpoim-Moreira |
| collection | DOAJ |
| description | Endometrosis negatively affects endometrial function and fertility in mares, due to excessive deposition of type I (COL1) and type III (COL3) collagens. The pro-fibrotic transforming growth factor (TGF-β1) induces myofibroblast differentiation, characterized by α-smooth muscle actin (α-SMA) expression, and collagen synthesis. In humans, fibrosis has been linked to epigenetic mechanisms. To the best of our knowledge, this has not been described in mare endometrium. Therefore, this study aimed to investigate the in vitro epigenetic regulation in TGF-β1-treated mare endometrial fibroblasts and the use of 5-aza-2′-deoxycytidine (5-aza-dC), an epigenetic modifier, as a putative treatment option for endometrial fibrosis. Methods and Results: The in vitro effects of TGF-β1 and of 5-aza-dC on DNA methyltransferases (<i>DNMT1</i>, <i>DNMT3A,</i> and <i>DNMT3B</i>), <i>COL1A1</i>, <i>COL3A1</i>, and <i>α-SMA</i> transcripts were analyzed in endometrial fibroblasts, and COL1 and COL3 secretion in a co-culture medium. TGF-β1 upregulated <i>DNMT3A</i> transcripts and collagen secretion. In TGF-β1-treated endometrial fibroblasts, DNA methylation inhibitor 5-aza-dC decreased collagen transcripts and secretion, but not <i>α-SMA</i> transcripts. Conclusion: These findings suggest a possible role of epigenetic mechanisms during equine endometrial fibrogenesis. The in vitro effect of 5-aza-dC on collagen reduction in TGF-β1-treated fibroblasts highlights this epigenetic involvement. This may pave the way to different therapeutic approaches for endometrosis. |
| first_indexed | 2024-03-11T05:44:24Z |
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| issn | 2076-2615 |
| language | English |
| last_indexed | 2024-03-11T05:44:24Z |
| publishDate | 2023-03-01 |
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| record_format | Article |
| series | Animals |
| spelling | doaj.art-fd32d49ec2304aacbad0281215f9ad182023-11-17T16:14:19ZengMDPI AGAnimals2076-26152023-03-01137121210.3390/ani130712125-Aza-2′-Deoxycytidine (5-Aza-dC, Decitabine) Inhibits Collagen Type I and III Expression in TGF-β1-Treated Equine Endometrial FibroblastsJoana Alpoim-Moreira0Anna Szóstek-Mioduchowska1Magda Słyszewska2Maria Rosa Rebordão3Dariusz J. Skarzynski4Graça Ferreira-Dias5CIISA—Center for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, PortugalInstitute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, PolandInstitute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, PolandCIISA—Center for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, PortugalDepartment of Animal Reproduction with Large Animal Clinic, Faculty of Veterinary Medicine, University of Environmental and Live Sciences, 50-366 Wrocław, PolandCIISA—Center for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, PortugalEndometrosis negatively affects endometrial function and fertility in mares, due to excessive deposition of type I (COL1) and type III (COL3) collagens. The pro-fibrotic transforming growth factor (TGF-β1) induces myofibroblast differentiation, characterized by α-smooth muscle actin (α-SMA) expression, and collagen synthesis. In humans, fibrosis has been linked to epigenetic mechanisms. To the best of our knowledge, this has not been described in mare endometrium. Therefore, this study aimed to investigate the in vitro epigenetic regulation in TGF-β1-treated mare endometrial fibroblasts and the use of 5-aza-2′-deoxycytidine (5-aza-dC), an epigenetic modifier, as a putative treatment option for endometrial fibrosis. Methods and Results: The in vitro effects of TGF-β1 and of 5-aza-dC on DNA methyltransferases (<i>DNMT1</i>, <i>DNMT3A,</i> and <i>DNMT3B</i>), <i>COL1A1</i>, <i>COL3A1</i>, and <i>α-SMA</i> transcripts were analyzed in endometrial fibroblasts, and COL1 and COL3 secretion in a co-culture medium. TGF-β1 upregulated <i>DNMT3A</i> transcripts and collagen secretion. In TGF-β1-treated endometrial fibroblasts, DNA methylation inhibitor 5-aza-dC decreased collagen transcripts and secretion, but not <i>α-SMA</i> transcripts. Conclusion: These findings suggest a possible role of epigenetic mechanisms during equine endometrial fibrogenesis. The in vitro effect of 5-aza-dC on collagen reduction in TGF-β1-treated fibroblasts highlights this epigenetic involvement. This may pave the way to different therapeutic approaches for endometrosis.https://www.mdpi.com/2076-2615/13/7/1212endometrosismarecollagenepigeneticsDNMTsfibroblasts |
| spellingShingle | Joana Alpoim-Moreira Anna Szóstek-Mioduchowska Magda Słyszewska Maria Rosa Rebordão Dariusz J. Skarzynski Graça Ferreira-Dias 5-Aza-2′-Deoxycytidine (5-Aza-dC, Decitabine) Inhibits Collagen Type I and III Expression in TGF-β1-Treated Equine Endometrial Fibroblasts Animals endometrosis mare collagen epigenetics DNMTs fibroblasts |
| title | 5-Aza-2′-Deoxycytidine (5-Aza-dC, Decitabine) Inhibits Collagen Type I and III Expression in TGF-β1-Treated Equine Endometrial Fibroblasts |
| title_full | 5-Aza-2′-Deoxycytidine (5-Aza-dC, Decitabine) Inhibits Collagen Type I and III Expression in TGF-β1-Treated Equine Endometrial Fibroblasts |
| title_fullStr | 5-Aza-2′-Deoxycytidine (5-Aza-dC, Decitabine) Inhibits Collagen Type I and III Expression in TGF-β1-Treated Equine Endometrial Fibroblasts |
| title_full_unstemmed | 5-Aza-2′-Deoxycytidine (5-Aza-dC, Decitabine) Inhibits Collagen Type I and III Expression in TGF-β1-Treated Equine Endometrial Fibroblasts |
| title_short | 5-Aza-2′-Deoxycytidine (5-Aza-dC, Decitabine) Inhibits Collagen Type I and III Expression in TGF-β1-Treated Equine Endometrial Fibroblasts |
| title_sort | 5 aza 2 deoxycytidine 5 aza dc decitabine inhibits collagen type i and iii expression in tgf β1 treated equine endometrial fibroblasts |
| topic | endometrosis mare collagen epigenetics DNMTs fibroblasts |
| url | https://www.mdpi.com/2076-2615/13/7/1212 |
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