Endometriosis Knowledgebase


A repository for genes associated with endometriosis

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PMID 25207642
Gene Name MAPK8
Condition Endometriosis
Association Associated
Sex Female
Associated genes MAPK8, CDC6, NOTCH1, CREB1, ID1, ID3
Other associated phenotypes Endometriosis
The peritoneum is both a source and target of TGF-beta in women with endometriosis.

PLoS One. 2014 Sep 10;9(9):e106773. doi: 10.1371/journal.pone.0106773.

Young, Vicky J| Brown, Jeremy K| Saunders, Philippa T K| Duncan, W Colin| Horne, Andrew W

MRC Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom.| MRC Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Ki

Transforming growth factor-beta (TGF-beta) 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-beta and if peritoneal TGF-beta 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-beta1, 2 and 3 protein concentrations were measured in the peritoneal fluid. TGF-beta1 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-beta expression, reception and signalling by immunohistochemistry, qRT-PCR and a TGF-beta signalling PCR array. TGF-beta1 was increased in the peritoneal fluid of women with endometriosis compared to those without disease (P<0.05) and peritoneal mesothelial cells secrete TGF-beta1 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-beta-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-beta1 and this is enhanced around endometriosis lesions. The expression of TGF-beta-regulated genes is altered in the peritoneum of women with endometriosis and this may promote an environment favorable to lesion formation.

Mesh Terms: Adolescent| Adult| Ascitic Fluid/metabolism| Case-Control Studies| Endometriosis/genetics/*metabolism/pathology| Epithelium/metabolism/pathology/secretion| Female| Gene Expression Profiling| Humans| Middle Aged| Peritoneum/*metabolism/pathology|