ID2 mediates the transforming growth factor-β1-induced Warburg-like effect seen in the peritoneum of women with endometriosis

• Published in: Molecular human reproduction 2016-09, Vol.22 (9), p.648-654
• Main Authors: Young, Vicky J, Ahmad, Syed F, Brown, Jeremy K, Duncan, W Colin, Horne, Andrew W
• Format: Article
• Language: English
• Subjects: Cell Line; Endometriosis - metabolism; Epithelium - drug effects; Epithelium - metabolism; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Immunoblotting; Immunohistochemistry; In Vitro Techniques; Inhibitor of Differentiation Protein 2 - genetics; Inhibitor of Differentiation Protein 2 - metabolism; Peritoneum - drug effects; Peritoneum - metabolism; RNA, Small Interfering; Transforming Growth Factor beta1 - pharmacology
• ISSN: 1360-9947; 1460-2407
• DOI: 10.1093/molehr/gaw045

Is inhibitor of DNA-binding protein 2 (ID2) a mediator of the transforming growth factor (TGF)-β1-induced Warburg-like effect seen in the peritoneum of women with endometriosis? The TGF-β1-induced changes in the metabolic phenotype of peritoneal mesothelial cells from women with endometriosis are mediated through the ID2 pathway. TGF-β1 induces the metabolic conversion of glucose to lactate via aerobic glycolysis (the 'Warburg effect') in the peritoneum of women with endometriosis, through increased expression of the transcription factor hypoxia inducible factor α (HIF-1α). ID proteins are transcriptional targets of TGF-β1. Expression of ID2 was investigated in luteal phase peritoneal biopsies from women with regular menstrual cycles, with and without endometriosis (n = 8-10 each group) by quantitative RT-PCR (qRT-PCR) and immunohistochemistry. ID2 mRNA expression in primary human peritoneal mesothelial cells (HPMC) and immortalized mesothelial cells (MeT-5A) was assessed by qRT-PCR (n = 6). The effects of TGF-β1 and ID2 siRNA on HIF-1α mRNA expression and lactate secretion was assessed using qRT-PCR and a colorimetric lactate assay. ID2 is localized to peritoneal mesothelial and stromal cells of women with and without endometriosis. ID2 mRNA expression is lower in peritoneum adjacent to the endometriosis lesions compared to distal sites (P