Abstract
Interleukin (IL)-34 plays a critical role in cell proliferation, differentiation, apoptosis, angiogenesis, inflammation and immunoregulation. Numerous diseases can be attributed to the dysregulation of IL-34 signaling. This study was performed to investigate the function of IL-34 in the pathogenesis of endometriosis. Firstly, by enzyme linked immunoabsorbent assay, we found that IL-34, VEGF, MMP-2 and MMP-9 were increased in the sera of patients with endometriosis. Secondly, exposure to IL-34 promoted the proliferation, migration and invasion of eutopic endometrial stromal cells (ESCs). Additionally, stimulation with IL-34 up-regulated colony-stimulating factor 1 receptor (CSF1R), p-JAK3, p-STAT6, VEGF, MMP-2 and MMP-9 in these eutopic ESCs. Treatment with AS1517499, an inhibitor of STAT6, remarkably abrogated the alterations induced by IL-34. A Chromatin immunoprecipitation (ChIP) assay demonstrated binding of STAT6 to the IL-34 promoter, further implicating STAT6 in IL-34 signaling. Notably, reverse results were obtained in ectopic ESCs with the application of an IL-34 neutralizing antibody. In vivo, AS1517499 suppressed the maintenance of endometriosis lesions in rats. In summary, autocrine production of IL-34, mediated by STAT6, promoted the development of endometriosis in vitro and in vivo through the CSF1R/JAK3/STAT6 pathway. Our research reveals the function of IL-34 in endometriosis, which may provide insight into novel therapeutic strategies for endometriosis.
Highlights
Endometriosis, a gynecological disease in which endometrial tissues are found outside the uterine cavity, such as on the ovary and pelvic peritoneum, commonly occurs in women of reproductive age[1,2,3]
We detected the serum levels of proteins associated with cell proliferation, angiogenesis, and epithelial-mesenchymal transition processes which are closely related to the pathogenesis of endometriosis, such as VEGF, MMP-2 and MMP-9,21–23, by Enzyme linked immunoabsorbent assay (ELISA)
The results showed that VEGF, MMP-2 and MMP-9 were elevated in the sera of the patients suffering from endometriosis (Fig. 1C–E)
Summary
Endometriosis, a gynecological disease in which endometrial tissues are found outside the uterine cavity, such as on the ovary and pelvic peritoneum, commonly occurs in women of reproductive age[1,2,3]. Pain relief is the primary purpose of treatment. Pharmacotherapies, such as the application of oral contraceptives or gonadotropin-releasing hormone agonists, and surgical resection of the endometriosis lesions are the main treatment options. Endometriosis is an estrogen-dependent inflammatory disease[9]. Mounting research suggests that cytokine-mediated innate immunity is involved in the pathogenesis of endometriosis[10,11,12]. Interleukin (IL)−17 facilitated the formation and persistence of endometriosis lesions by increasing angiogenesis and the secretion of pro-inflammatory cytokines[13]. We hypothesized that IL-34 may play an important role as a multifunctional inflammatory cytokine in the pathogenesis and persistence of endometriotic lesions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
