endothelin-1 and Endometriosis

MiR-370-3p has been demonstrated to be downregulated in patients with endometriosis (EM). However, its role and molecular mechanisms in the progression of EM remain unclear. Real-time polymerase chain reaction was used to measure the expression of miR-370-3p and endothelin-1 (EDN1) in patients with or without EM. After miR-370-3p overexpression or knockdown in ectopic endometrial hEM15A cells, the changes in the proliferation, apoptosis, and migration and invasion capacities were detected by using cell counting kit-8, flow cytometry, and transwell methods. The interplay between miR-370-3p and EDN1 was confirmed by a luciferase reporter assay. Patients with EM showed adverse expression of EDN1 and miR-370-3p, especially in eutopic endometrium and ectopic endometrium. MiR-370-3p inhibited the proliferation, metastasis, and invasion capacities of hEM15A cells and promoted apoptosis. Investigation of its molecular mechanism revealed that miR-370-3p targeted EDN1 to influence the biological functions of hEM15A cells. MiR-370-3p represented as a therapeutic target for EM treatment.

Topics: Adolescent; Adult; Cells, Cultured; Endometriosis; Endometrium; Endothelin-1; Female; Humans; MicroRNAs; Middle Aged; Stromal Cells; Young Adult

Endometriosis is a gynaecological disease exhibiting severe pelvic pain, but the mechanism of pain production remains unknown. Bradykinin (BK) is known as an inflammatory mediator, and shows elevated levels in inflammatory diseases such as rheumatoid arthritis. In the present study, we evaluated whether BK is involved in endometriosis-related pain.. Endometriotic lesions were used for immunohistochemistry. Primary cultures of endometriotic stromal cells (ESC) were stimulated with IL-1β and/or BK. Quantitative RT-PCR was used to evaluate the mRNA expressions of BK receptors (BKR) and endothelin-1 in ESC. The concentration of endothelin-1 in cystic fluid of endometrioma or non-endometrioma was measured with ELISA. The conditioned medium of ESC stimulated with IL-1β and/or BK was injected intraplantarly in mice, and evaluated whether pain-related licking behaviour was elicited.. The expressions of BK and BKR in endometriotic lesions were observed by immunohistochemistry. In vitro experiments showed that IL-1β induced BKR-B1 and B2 on ESC. Activation of these receptors by BK significantly induced endothelin-1 expression in ESC, which was negated completely by HOE-140, a BKR-B2 antagonist. The cystic fluid of endometrioma contained higher amount of endothelin-1 compared to non-endometrioma. Intraplantar injection of the conditioned medium of ESC treated with IL-1β and BK significantly induced licking behaviour, which was suppressed with BQ-123, an endothelin type-A receptor antagonist.. The present study demonstrated the presence and the function of the BK axis in endometriosis, and established a potential new therapy target for endometriosis-related pain.. The present study demonstrated (1) the presence and the function of the BK system in endometriosis, (2) activation of BKR induced endothelin-1 in endometriotic lesion and (3) blocking endothelin-1 was effective to decrease pain.

Topics: Animals; Behavior, Animal; Bradykinin; Bradykinin B2 Receptor Antagonists; Case-Control Studies; Cells, Cultured; Culture Media, Conditioned; Cyst Fluid; Endometriosis; Endothelin-1; Female; Humans; Interleukin-1beta; Mice; Ovarian Diseases; Pain; Peritoneal Diseases; Receptors, Bradykinin; RNA, Messenger; Stromal Cells

To investigate the expression of endothelin-1 (ET-1) and its receptors (ET(A)R, ET(B)R) in patients with endometriosis and to explore the possible role of them in the pathogenesis of endometriosis.. The tissues of ectopic and eutopic endometrium were collected from 48 cases of endometriosis (EM), while the control samples were eutopic endometrium from 13 cases of cervical intraepithelial neoplasia (CIN). The expressions and locations of ET-1, ET(A)R, ET(B)R were measured by immunohistochemical staining.. The expression levels of ET-1 and ET(A)R of EMs group, either in eutopic or in ectopic endometrium, were higher than those of the control group (All P<0.01). Moreover, the expression levels of ET-1 and ETAR in eutopic endometrium were higher than those in ectopic endometrium. There were significant correlations between the expression of ET-1 and ETAR in EMs group, either for eutopic or for ectopic endometrium (r=0.970, 0.968 respectively, All P<0.05). There was no significant difference in the expression level of ET(B)R among eutopic endometrium of EMs, ectopic endometrium of Ems and eutopic endometrium of control group (All P>0.05). There was no significant difference in the expression level of ET-1, ET(A)R and ET(B)R in proliferative phase and secretory phase in both EMs group and control group (All P>0.05). The expression levels of ET-1, ET(A)R and ET(B)R were not associated with r-AFS staging of endometriosis (All P>0.05).. By the way of combining ET(A)R, ET-1 may play a important role in the pathogenesis of endometriosis.

Topics: Adult; Endometriosis; Endometrium; Endothelin-1; Female; Humans; Middle Aged; Receptor, Endothelin A