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.
Sci Rep. 2015 Nov 18;5:16859. doi: 10.1038/srep16859.
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.
血管内皮生长因子A（VEGF-A）是一种血管生成因子，在子宫内膜异位症女性的腹腔液中含量升高。细胞因子转化生长因子β1（TGF-β1）被认为在子宫内膜异位症病灶的形成中起作用。DNA结合抑制因子（ID）蛋白是TGF-β1的转录靶点，ID1在肿瘤血管生成过程中参与VEGF-A的调节。在此，我们确定在子宫内膜异位症女性中，VEGF-A的腹腔表达是否通过ID1途径受TGF-β1调控。通过酶联免疫吸附测定法（ELISA）检测腹腔液中的VEGF-A（n = 16）。通过免疫组织化学、定量逆转录聚合酶链反应（qRT-PCR）和ELISA检测腹腔活检组织（n = 13）、原代腹腔间皮细胞和永生化间皮细胞（MeT5A）中的VEGF-A和ID1表达。子宫内膜异位症女性腹腔液中的VEGF-A升高，其水平与TGF-β1浓度相关（P < 0.05）。VEGF-A免疫定位于腹腔间皮，TGF-β1可增加间皮细胞中VEGFA mRNA（P < 0.05）和蛋白水平（P < 0.05）。子宫内膜异位症女性腹膜中的ID1增加，TGF-β1可增加间皮细胞中ID1 mRNA的浓度（P < 0.05）。在MeT5A细胞中通过小干扰RNA（siRNA）证实了VEGF-A通过ID1进行调控（P < 0.05）。我们的数据支持ID1在子宫内膜异位症病理生理学中的作用，作为TGFβ1依赖性上调VEGF-A的效应器，并突出了一个新的潜在治疗靶点。
