Overexpression of Four Joint Box-1 Protein (FJX1) in Eutopic Endometrium From Women With Endometriosis.

The four jointed box 1 (FJX1) is a regulator of angiogenesis, and the levels of FJX1 are increased in several types of cancer. Angiogenesis plays a critical role in endometrial growth as well as in several gynecologic disorders including endometriosis. However, the function of FJX1 has not been studied in endometriosis. Therefore, we examined the levels of FJX1 in eutopic endometrium from women with or without endometriosis. The levels of FJX1 protein did not change in endometrial cells during the menstrual cycle in endometrium from women without endometriosis. However, its levels were significantly higher in the secretory phase of the eutopic endometrium from women with endometriosis when compared to women without endometriosis. Hypoxia-inducible factor-1α (HIF1α) is known as a key mediator of endometriosis by regulating genes essential to estrogen production, angiogenesis, proliferation, inflammation, and extracellular invasion. It has been reported that FJX1 induces an increase in HIF1α through posttranslational stabilization. The results of our Western blot analysis reveal a significant positive correlation between FJX1 and HIF1α proteins in endometrium of women with and without endometriosis. This overexpression of FJX1 was confirmed by sequential analysis of the eutopic endometrium during endometriosis progression, using an induced model of endometriosis in the baboon. Therefore, our results suggest that high levels of FJX1 proteins may play an important role in the pathogenesis of endometriosis.