title: The peritoneum is both a source and target of TGF-β in women with endometriosis.
abstract: 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.
authors.affiliation: MRC Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom.
authors.forename: Vicky J
authors.initials: VJ
authors.lastname: Young
authors.affiliation: MRC Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom.
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Brown
authors.affiliation: MRC Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom.
authors.forename: Philippa T K
authors.initials: PT
authors.lastname: Saunders
authors.affiliation: MRC Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom.
authors.forename: W Colin
authors.initials: WC
authors.lastname: Duncan
authors.affiliation: MRC Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Horne
mesh_terms: D000293:Adolescent; D000328:Adult; D001202:Ascitic Fluid / Q000378:metabolism; D016022:Case-Control Studies; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D010537:Peritoneum / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D066246:ErbB Receptors