Abstract
Although endometriosis is a benign disease characterized by the presence of endometrial tissues outside the uterus, ectopic endometrial cells can exhibit malignant biological behaviors. Retinol-binding protein4 (RBP4) is a novel adipocyte-derived cytokine, which has important roles in regulating insulin sensitivity and energy metabolism. RBP4 is a potent modulator of gene transcription, and acts by directly controlling cell growth, invasiveness, proliferation and differentiation. Here, we evaluated the possible role of RBP4 in the pathogenesis of endometriosis. We compared the levels of RBP4 in the tissues and peritoneal fluid (PF) of women with and without endometriosis and evaluated the in vitro effects of RBP4 on the viability, invasiveness, and proliferation of endometrial stromal cells (ESCs). RBP4 levels were significantly higher in the PF of the women in the endometriosis group than in the controls. RBP4 immunoreactivity was significantly higher in the ovarian endometriomas of women with advanced stage endometriosis than those of controls. In vitro treatment with human recombinant-RBP4 significantly increased the viability, bromodeoxyuridine expression, and invasiveness of ESCs. Transfection with RBP4 siRNA significantly reduced ESC viability and invasiveness. These findings suggest that RBP4 partakes in the pathogenesis of endometriosis by increasing the viability, proliferation and invasion of endometrial cells.
Highlights
Among those soluble proteins significantly increased in peritoneal fluid (PF) in patients with endometriosis compared with controls, we found that the increase in the levels of Retinol-binding protein4 (RBP4) in endometriosis has not been reported to date
The levels of RBP4 in the PF were significantly higher in the endometriosis group compared with the control group (P < 0.05) (Figure 1C)
RBP4 duced from adipose tissues, and the serum RBP4 levels have been shown to be elevated activates andmice induces release of pro-inflammatory cytokine, which leads in obese, macrophages insulin-resistant and the humans
Summary
Endometriosis is a common chronic inflammatory disease that is characterized by the presence of endometrial glands and stroma outside the uterine cavity. The pathogenesis of endometriosis has not been completely elucidated, the most popular and widely accepted etiology is Sampson’s theory of retrograde menstruation [3]. This theory describes how viable endometrial tissue can spread into the peritoneal cavity through the fallopian tubes during menstruation and elicit an inflammatory response. As all women with reflux menstruation do not have endometriosis, the retrograde menstruation theory alone cannot explain all cases of endometriosis
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