Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030794 (pelvic pain)
 4,056 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endometriosis is a common incurable inflammatory disorder that is associated with debilitating pelvic pain in women. Macrophages are central to the pathophysiology of endometriosis: they dictate the growth and vascularization of endometriosis lesions and more recently have been shown to promote lesion innervation. The aim of this study was to determine the mechanistic role of macrophages in producing pain associated with endometriosis. Herein, we show that macrophage depletion in a mouse model of endometriosis can reverse abnormal changes in pain behavior. We identified that disease-modified macrophages exhibit increased expression of IGF-1 in an in vitro model of endometriosis-associated macrophages and confirmed expression by lesion-resident macrophages in mice and women. Concentrations of IGF-1 were elevated in peritoneal fluid from women with endometriosis and positively correlate with their pain scores. Mechanistically, we demonstrate that macrophage-derived IGF-1 promotes sprouting neurogenesis and nerve sensitization in vitro. Finally, we show that the Igf-1 receptor inhibitor linsitinib reverses the pain behavior observed in mice with endometriosis. Our data support a role for macrophage-derived IGF-1 as a key neurotrophic and sensitizing factor in endometriosis, and we propose that therapies that modify macrophage phenotype may be attractive therapeutic options for the treatment of women with endometriosis-associated pain.-Forster, R., Sarginson, A., Velichkova, A., Hogg, C., Dorning, A., Horne, A. W., Saunders, P. T. K., Greaves, E. Macrophage-derived insulin-like growth factor-1 is a key neurotrophic and nerve-sensitizing factor in pain associated with endometriosis.
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PMID:Macrophage-derived insulin-like growth factor-1 is a key neurotrophic and nerve-sensitizing factor in pain associated with endometriosis. 3201 99

Endometriosis (Ems) is a common gynecological disease with the characteristics of infertility, pelvic pain, and sexual intercourse difficulty. Our present study aimed to investigate the effect of miR-199a-5p on cell mobility and epithelial-mesenchymal transition (EMT) in Ems. Ectopic endometrial stromal cells (EcSCs) and control endometrial stromal cells (CSCs) were isolated in our in vitro experiments. The level of miR-199a-5p in EcSCs was found much lower than that in CSCs. Besides, miR-199a-5p mimic suppressed the invasion and migration ability of EcSCs. At the same time, EMT was also found to be suppressed by miR-199a-5p mimic in EcSCs. Our further bioinformatics analysis and luciferase reporter assay revealed that ZEB1, a marker of EMT, was a direct target of miR-199a-5p. In addition, the combination of pcDNA3.1-ZEB1 weakened the inhibiting effect of miR-199a-5p mimic on the mobility and EMT of EcSCs. What is more, the PI3K/Akt/mTOR signal pathway was demonstrated to be inactivated by miR-199a-5p mimic. And then, the inducer of PI3K/Akt/mTOR signal pathway, IGF-1, abolished the effect of miR-199a-5p mimic on Ems progression. At last, an Ems rat model was established, and we found that miR-199a-5p agomir effectively suppressed the expression of vascular endothelial growth factor (VEGF) and EMT in vivo. The PI3K/Akt/mTOR signal pathway was also inactivated by miR-199a-5p agomir in our Ems rat model. Taken together, we concluded that miR-199a-5p targeted ZEB1 to inhibit the EMT of ovarian ectopic endometrial stromal cells via PI3K/Akt/mTOR signal pathway in vitro and in vivo, advancing our understanding of miR-199a-5p as regulators of Ems progression and making contribution to the treatment of Ems.
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PMID:MiR-199a-5p Targets ZEB1 to Inhibit the Epithelial-Mesenchymal Transition of Ovarian Ectopic Endometrial Stromal Cells Via PI3K/Akt/mTOR Signal Pathway In Vitro and In Vivo. 3204 78