Interleukin-6 (IL-6) activates the NOTCH1 signaling pathway through E-proteins in endometriotic lesions

Context: NOTCH signaling is activated in endometriotic lesions but the exact mechanisms remains unclear. Interleukin-6 (IL-6), which is increased in the peritoneal fluid of women with endometriosis, induces NOTCH1 through E-proteins including E2A and HEB in cancer development.

Objective: To study the role of E-proteins in inducing NOTCH1 expression under the regulation of IL-6 in endometriosis.

Setting and Design: The expression of E2A, HEB and NOTCH1 was first investigated in endometrium of women with endometriosis and the baboon model of endometriosis. Regulation of E-proteins and NOTCH1 expression was examined after IL-6 stimulation and siRNA mediated inhibition of E2A or/and HEB in human endometriotic epithelial cells (12Z) in vitro, and subsequent following in vivo IL-6 treatment in the mouse model of endometriosis in vivo.

Results: E2A, HEB and NOTCH1 were significantly upregulated in glandular epithelium (GE) of ectopic endometrium compared to eutopic endometrium in both...