Abstract
BackgroundEndometriosis is an estrogen-dependent disease causing pelvic pain and infertility in 10% of reproductive-aged women. Despite a long history of the disease the pathogenesis of endometriosis is poorly understood. It is known that the expression of several proteins is either up or down regulated during endometriosis, but their precise role remains to be determined. DJ-1 is one such protein that is upregulated in eutopic endometrium of women having endometriosis suggesting that DJ-1 may be involved in the pathogenesis of endometriosis.Methodology and Principal FindingsThe role of DJ-1 in the pathogenesis of endometriosis was investigated. For this purpose the influence of DJ-1 on endometrial cell survival, attachment, proliferation, migration, and invasion either by overexpressing DJ-1 in normal endometrial cells or by knocking down DJ-1 expression in endometriotic cells using siRNA was investigated. The results indicated that DJ-1 protects endometrial cells from oxidative stress mediated apoptosis. Overexpression of DJ-1 in normal endometrial epithelial cells increases the adhesion on collagen type IV. However, no significant difference was observed incase of stromal cells. It was further demonstrated that DJ-1 regulates cell proliferation, migration, and invasion in normal endometrial and endometriotic epithelial cells whereas in the case of normal endometrial and endometriotic stromal cells, it regulates cell proliferation and invasion but not migration. Furthermore, the present study also indicated that DJ-1 regulates these cellular processes by modulating PI3K/Akt pathway by interacting and negatively regulating PTEN.ConclusionsAbnormally high levels of DJ-1 expression may be involved in endometriosis, possibly by stimulating endometrial cell survival, proliferation, migration, and invasion.
Highlights
Endometriosis is a complex gynecological disease which occurs in 10% of reproductive age women
Abnormally high levels of DJ-1 expression may be involved in endometriosis, possibly by stimulating endometrial cell survival, proliferation, migration, and invasion
In this study it was observed that DJ-1 protein is upregulated in eutopic endometrium of women having endometriosis compared with controls. These findings suggest that DJ-1 may be involved in the pathogenesis of endometriosis
Summary
Endometriosis is a complex gynecological disease which occurs in 10% of reproductive age women. The disease is characterized by the presence and growth of endometrial tissue outside the uterus, causing pelvic pain, and infertility [1]. The formation of a lesion depends on the survival, attachment, growth, neoangiogenesis, and invasion of the endometrial cells at the ectopic sites [2]. This may be due to abnormalities of the eutopic endometrium itself, predisposing the cells to survive and implant ectopically [3]. Endometriosis is an estrogen-dependent disease causing pelvic pain and infertility in 10% of reproductiveaged women. DJ-1 is one such protein that is upregulated in eutopic endometrium of women having endometriosis suggesting that DJ-1 may be involved in the pathogenesis of endometriosis
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