Abstract
AimHigh mobility group box (HMGB)-1 has been implicated in endometriosis due to the important regulatory roles of inflammation in endometriosis. The aim of the present study was to explore the roles of HMGB-1 in endometriosis and to elucidate the underlying mechanism.MethodsEndometrial specimens were collected from women with endometriosis and healthy volunteers. Immunohistochemistry staining was used to determine the expression patterns and localization of HMGB-1 in the normal, eutopic and ectopic endometrial tissues. Western blotting and qRT-PCR were used to determine the mRNA and protein levels of inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-1β], autophagy-related markers [beclin-1, autophagy-related (atg)13, microtubule-associated protein light chain (LC)3-I, LC-II and p62] and HMGB-1, respectively. Spearman’s rank correlation analysis was employed to investigate the correlation between HMGB-1 with inflammatory cytokines and beclin-1. Besides, human endometrial stromal cells (HESCs) were isolated from ectopic endometrium and subsequently transfected with shRNA against HMGB-1. After the transfected cells were subjected to hypoxia, ELISA was used to determine the levels of HMGB-1 and inflammatory cytokines in the cell supernatant. Western blotting was used to determine the expression levels of autophagy-related markers in the cells.ResultsPositive correlations were observed between HMGB-1 and the inflammatory cytokines. In addition, a positive correlation was also identified between HMGB-1 and beclin-1 in the ectopic endometrium. Further results demonstrated that autophagy-related markers beclin-1, atg13 and p62 were significantly upregulated in the ectopic endometrium. In addition, HMGB-1 knockdown suppressed the levels of inflammatory cytokines IL-6, TNF-α and IL-1β and autophagy-related markers beclin-1 and atg13, while upregulated p62 in HESCs under hypoxic condition.ConclusionKnockdown of HMGB-1 under hypoxic condition regulated inflammatory cytokines and autophagy-related markers. HMGB-1 might contribute to the development of endometriosis in part through regulating inflammatory response and autophagy.
Highlights
Endometriosis is a chronic disorder of the endometrium [1, 2]
We found that the levels of IL-6, TNF-a, and IL-1b were significantly increased in the ectopic endometrium as compared to the normal and eutopic endometrial tissues (Figures 2A–C)
Our results revealed that HMGB-1 was upregulated in ectopic endometrium, which was positively correlated with inflammatory cytokines IL-6, TNF-a, and IL-1b, as well as autophagy-related protein beclin-1, suggesting that HMGB-1 might be involved in endometriosis
Summary
Endometriosis is a chronic disorder of the endometrium [1, 2]. The abnormal growth and infiltration of endometrial cells, including endometrial epithelial cells and stromal cells in the endometrium, into the deep endometriosis tissues causes the formation of nodules and masses in the endometrium [2, 3]. Endometriosis is one of the most important risk factors of chronic pelvic pain, dysmenorrhea and infertility [4, 5]. Endometriosis affects around 15% of women of reproductive age, while 30 to 50% of infertile women suffer from endometriosis [6]. Inflammation plays an important role in endometriosis [4]. Elevated inflammatory cytokines and mediators in the peritoneal fluid, which are frequently found in patients with endometriosis [7], induce endometriotic symptoms
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