The peritoneum is both a source and target of TGF-β in women with endometriosis.
Transforming growth factor-β (TGF-β) is believed to play a major role in the aetiology of peritoneal endometriosis. We aimed to determine if the peritoneum is a source of TGF-β and if peritoneal TGF-β expression, reception or target genes are altered in women with endometriosis. Peritoneal fluid, pe...
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| Format: | Article |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0106773 |
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| author | Vicky J Young Jeremy K Brown Philippa T K Saunders W Colin Duncan Andrew W Horne |
| author_facet | Vicky J Young Jeremy K Brown Philippa T K Saunders W Colin Duncan Andrew W Horne |
| author_sort | Vicky J Young |
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| description | Transforming growth factor-β (TGF-β) is believed to play a major role in the aetiology of peritoneal endometriosis. We aimed to determine if the peritoneum is a source of TGF-β and if peritoneal TGF-β expression, reception or target genes are altered in women with endometriosis. Peritoneal fluid, peritoneal bushings and peritoneal biopsies were collected from women with and without endometriosis. TGF-β1, 2 and 3 protein concentrations were measured in the peritoneal fluid. TGF-β1 was measured in mesothelial cell conditioned media. Control peritoneum and peritoneum prone to endometriosis (within Pouch of Douglas) from women without disease (n = 16) and peritoneum distal and adjacent to endometriosis lesions in women with endometriosis (n = 15) and were analysed for TGF-β expression, reception and signalling by immunohistochemistry, qRT-PCR and a TGF-β signalling PCR array. TGF-β1 was increased in the peritoneal fluid of women with endometriosis compared to those without disease (P<0.05) and peritoneal mesothelial cells secrete TGF-β1 in-vitro. In women with endometriosis, peritoneum from sites adjacent to endometriosis lesions expressed higher levels of TGFB1 mRNA when compared to distal sites (P<0.05). The TGF-β-stimulated Smad 2/3 signalling pathway was active in the peritoneum and there were significant increases (P<0.05) in expression of genes associated with tumorigenesis (MAPK8, CDC6), epithelial-mesenchymal transition (NOTCH1), angiogenesis (ID1, ID3) and neurogenesis (CREB1) in the peritoneum of women with endometriosis. In conclusion, the peritoneum, and in particular, the peritoneal mesothelium, is a source of TGF-β1 and this is enhanced around endometriosis lesions. The expression of TGF-β-regulated genes is altered in the peritoneum of women with endometriosis and this may promote an environment favorable to lesion formation. |
| format | Article |
| id | doaj-art-196ed9fb68204d2bac0cbde5e1997c9b |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-196ed9fb68204d2bac0cbde5e1997c9b2025-08-20T02:22:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10677310.1371/journal.pone.0106773The peritoneum is both a source and target of TGF-β in women with endometriosis.Vicky J YoungJeremy K BrownPhilippa T K SaundersW Colin DuncanAndrew W HorneTransforming growth factor-β (TGF-β) is believed to play a major role in the aetiology of peritoneal endometriosis. We aimed to determine if the peritoneum is a source of TGF-β and if peritoneal TGF-β expression, reception or target genes are altered in women with endometriosis. Peritoneal fluid, peritoneal bushings and peritoneal biopsies were collected from women with and without endometriosis. TGF-β1, 2 and 3 protein concentrations were measured in the peritoneal fluid. TGF-β1 was measured in mesothelial cell conditioned media. Control peritoneum and peritoneum prone to endometriosis (within Pouch of Douglas) from women without disease (n = 16) and peritoneum distal and adjacent to endometriosis lesions in women with endometriosis (n = 15) and were analysed for TGF-β expression, reception and signalling by immunohistochemistry, qRT-PCR and a TGF-β signalling PCR array. TGF-β1 was increased in the peritoneal fluid of women with endometriosis compared to those without disease (P<0.05) and peritoneal mesothelial cells secrete TGF-β1 in-vitro. In women with endometriosis, peritoneum from sites adjacent to endometriosis lesions expressed higher levels of TGFB1 mRNA when compared to distal sites (P<0.05). The TGF-β-stimulated Smad 2/3 signalling pathway was active in the peritoneum and there were significant increases (P<0.05) in expression of genes associated with tumorigenesis (MAPK8, CDC6), epithelial-mesenchymal transition (NOTCH1), angiogenesis (ID1, ID3) and neurogenesis (CREB1) in the peritoneum of women with endometriosis. In conclusion, the peritoneum, and in particular, the peritoneal mesothelium, is a source of TGF-β1 and this is enhanced around endometriosis lesions. The expression of TGF-β-regulated genes is altered in the peritoneum of women with endometriosis and this may promote an environment favorable to lesion formation.https://doi.org/10.1371/journal.pone.0106773 |
| spellingShingle | Vicky J Young Jeremy K Brown Philippa T K Saunders W Colin Duncan Andrew W Horne The peritoneum is both a source and target of TGF-β in women with endometriosis. PLoS ONE |
| title | The peritoneum is both a source and target of TGF-β in women with endometriosis. |
| title_full | The peritoneum is both a source and target of TGF-β in women with endometriosis. |
| title_fullStr | The peritoneum is both a source and target of TGF-β in women with endometriosis. |
| title_full_unstemmed | The peritoneum is both a source and target of TGF-β in women with endometriosis. |
| title_short | The peritoneum is both a source and target of TGF-β in women with endometriosis. |
| title_sort | peritoneum is both a source and target of tgf β in women with endometriosis |
| url | https://doi.org/10.1371/journal.pone.0106773 |
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