title: Peritoneal VEGF-A expression is regulated by TGF-β1 through an ID1 pathway in women with endometriosis.
abstract: VEGF-A, an angiogenic factor, is increased in the peritoneal fluid of women with endometriosis. The cytokine TGF-β1 is thought to play a role in the establishment of endometriosis lesions. Inhibitor of DNA binding (ID) proteins are transcriptional targets of TGF-β1 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-β1 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-β1 concentrations (P < 0.05). VEGF-A was immunolocalized to peritoneal mesothelium and TGF-β1 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-β1 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 TGFβ1 dependent upregulation of VEGF-A, and highlights a novel potential therapeutic target.
authors.affiliation: MRC Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK.
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 EH16 4TJ, UK.
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ahmad
authors.affiliation: MRC Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK.
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 EH16 4TJ, UK.
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 EH16 4TJ, UK.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Horne
mesh_terms: D001202:Ascitic Fluid / Q000378:metabolism; D002478:Cells, Cultured; D004715:Endometriosis / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism*; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D051798:Inhibitor of Differentiation Protein 1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A