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5-Aza-20 -Deoxycytidine (5-Aza-dC, Decitabine) Inhibits Collagen Type I and III Expression in TGF-β1-Treated Equine Endometrial Fibroblasts
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Orientador(es)
Resumo(s)
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-20 -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 (DNMT1, DNMT3A, and DNMT3B), COL1A1, COL3A1, and α-SMA
transcripts were analyzed in endometrial fibroblasts, and COL1 and COL3 secretion in a co-culture
medium. TGF-β1 upregulated DNMT3A transcripts and collagen secretion. In TGF-β1-treated
endometrial fibroblasts, DNA methylation inhibitor 5-aza-dC decreased collagen transcripts and
secretion, but not α-SMA 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
Descrição
Research Areas: Agriculture ; Veterinary Sciences ; Zoology
Palavras-chave
Endometrosis mare collagen epigenetics DNMTs fibroblasts 5-aza-dC demethylating inhibitor
Contexto Educativo
Citação
Alpoim-Moreira J, Szóstek-Mioduchowska A, Słyszewska M, Rebordão MR, Skarzynski DJ, Ferreira-Dias G. 2023. 5-Aza-20 -Deoxycytidine (5-Aza-dC, Decitabine) Inhibits Collagen Type I and III Expression in TGF-β1-Treated Equine Endometrial Fibroblasts. Animals, 13(7):1212. DOI: https:// doi.org/10.3390/ani13071212
Editora
MDPI