Results
PMID | 26577912 |
Gene Name | ID1 |
Condition | Endometriosis |
Association |
Associated |
Population size | 29 |
Population details | 29 women with endometriosis |
Sex | Female |
Other associated phenotypes |
Endometriosis |
Sci Rep. 2015 Nov 18;5:16859. doi: 10.1038/srep16859. Young, Vicky J| Ahmad, Syed F| Brown, Jeremy K| Duncan, W Colin| Horne, Andrew W MRC Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK.| MRC Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK. VEGF-A, an angiogenic factor, is increased in the peritoneal fluid of women with endometriosis. The cytokine TGF-beta1 is thought to play a role in the establishment of endometriosis lesions. Inhibitor of DNA binding (ID) proteins are transcriptional targets of TGF-beta1 and ID1 has been implicated in VEGF-A regulation during tumor angiogenesis. Herein, we determined whether peritoneal expression of VEGF-A is regulated by TGF-beta1 through the ID1 pathway in women with endometriosis. VEGF-A was measured in peritoneal fluid by ELISA (n = 16). VEGF-A and ID1 expression was examined in peritoneal biopsies (n = 13), and primary peritoneal and immortalized mesothelial cells (MeT5A) by immunohistochemistry, qRT-PCR and ELISA. VEGF-A was increased in peritoneal fluid from women with endometriosis and levels correlated with TGF-beta1 concentrations (P < 0.05). VEGF-A was immunolocalized to peritoneal mesothelium and TGF-beta1 increased VEGFA mRNA (P < 0.05) and protein (P < 0.05) in mesothelial cells. ID1 was increased in peritoneum from women with endometriosis and TGF-beta1 increased concentrations of ID1 mRNA (P < 0.05) in mesothelial cells. VEGF-A regulation through ID1 was confirmed by siRNA in MeT5A cells (P < 0.05). Our data supports role for ID1 in the pathophysiology of endometriosis, as an effector of TGFbeta1 dependent upregulation of VEGF-A, and highlights a novel potential therapeutic target. Mesh Terms: Ascitic Fluid/metabolism| Cells, Cultured| Endometriosis/*genetics/*metabolism| Female| *Gene Expression Regulation/drug effects| Gene Knockdown Techniques| Humans| Inhibitor of Differentiation Protein 1/genetics/*metabolism| Peritoneum/cytology/m |