The efficacy of niclosamide on the intra-abdominal inflammatory environment in endometriosis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE147024 | GEO | 2022/11/14
REPOSITORIES: GEO
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Project description:The efficacy of niclosamide on the intra-abdominal inflammatory environment in endometriosis
| PRJNA612816 | ENA
Project description:Endometriosis, a common gynecological disease, causes chronic pelvic pain and infertility in women of reproductive age. Due to the limited efficacy of current therapies, a critical need exists to develop new treatments for endometriosis. Inflammatory dysfunction, instigated by abnormal macrophage (MΦ) function, contributes to disease development and progression. However, the fundamental role of the heterogeneous population of peritoneal MΦ and their potential druggable functions is uncertain. Here we report that GATA6-expressing large peritoneal MΦ (LPM) were increased in the peritoneal cavity following lesion induction. This was associated with increased cytokine and chemokine secretion in the peritoneal fluid (PF), as well as MΦ infiltration, vascularization and innervation in endometriosis-like lesions (ELL). Niclosamide, an FDA-approved anti-helminthic drug, was effective in reducing LPM number, but not small peritoneal MΦ (SPM), in the PF. Niclosamide also inhibits aberrant inflammation in the PF, ELL, pelvic organs (uterus and vagina) and dorsal root ganglion (DRG), as well as MΦ infiltration, vascularization and innervation in the ELL. PF from ELL mice stimulated DRG outgrowth in vitro, whereas the PF from niclosamide-treated ELL mice lacked the strong stimulatory nerve growth response. These results suggest LPM induce aberrant inflammation in endometriosis promoting lesion progression and establishment of the inflammatory environment that sensitizes peripheral nociceptors in the lesions and other pelvic organs, leading to increased hyperalgesia. Our findings provide the rationale for targeting LPM and their functions with niclosamide and its efficacy in endometriosis as a new non-hormonal therapy to reduce aberrant inflammation which may ultimately diminish associated pain.
| S-EPMC10777336 | biostudies-literature
Project description:We performed gene expression analysis human peritoneal endometriosis lesions, eutopic endometrium from endometriosis patients and peritoneum form endometriosis patients.The goal of the study was to analyse gene expression differences between peritoneal endometriosis lesion and eutopic endometrium and peritoneal endometriosis lesion and peritoneum.
2012-12-06 | E-MTAB-694 | biostudies-arrayexpress
Project description:Because niclosamide inhibits growth and progression of endometriotic lesions, we performed RNA-seq in order to identify genes whose expression is regulated by niclosamide in endometriotic lesions. Our results shown that niclosamide modulates several genes related to cell signaling, extracellular matrix, and inflammatory signaling.
2017-01-01 | GSE79698 | GEO
Project description:Endometriosis is a common gynecological disease of women in reproductive age, and is primarily thought to arise from retrograde menstruation and implantation of endometrium, mostly into the peritoneal cavity. The condition is characterized by a chronic, unresolved inflammatory process, within which oxidative stress likely plays a critical role. Although elevated reactive oxygen species (ROS) and oxidative stress have previously been postulated as being involved in endometriosis pathogenesis, we set out for a more systematic study to identify novel factors defining oxidative stress in ectopic peritoneal lesions. Using combined proteomic and transcriptomic approaches, we identified novel targets, including upregulated pro-oxidative enzymes such as amine oxidase 3/vascular adhesion protein 1 (AOC3/VAP1), as well as downregulated protective factors such as alkenal reductase PTGR1 or methionine sulfoxide reductase, supporting the observation of increased oxidative protein modification in ectopic lesions and peritoneal fluid. The observed ROS-derived 4-hydroxy-2-nonenal-induced interleukin (IL)-8 release from monocytes indicates a further pathomechanism, whereby elevated IL-8 levels promote further immune cell infiltration and angiogenesis in lesions.
2020-05-26 | PXD006553 | Pride
Project description:Endometriosis is characterized by growth of endometrial-like tissue outside of the uterus affecting many women during their reproductive age, causing years of pelvic pain and potential infertility. Its pathophysiology remains largely unknown, limiting early diagnosis and treatment. We characterized peritoneal and ovarian lesions at single-cell transcriptome resolution and compared to matched eutopic endometrium, control endometrium, and organoids derived from these tissues, generating data on over 122,000 cells across 14 individuals. We spatially localized many of the cell types using imaging mass cytometry. We identify a perivascular mural cell unique to the peritoneal lesions with dual roles in angiogenesis promotion and immune cell trafficking. We define an immunotolerant peritoneal niche, fundamental differences in eutopic endometrium and between lesions microenvironments, and an unreported progenitor-like epithelial cell subpopulation. Altogether, this study provides a holistic view of the endometriosis microenvironment representing a comprehensive cell atlas of the disease in hormonally treated patients, essential information for advancing therapeutics and diagnostics.
2022-05-05 | GSE179640 | GEO
Project description:We focus on the characterization of gene expression profiles in circulating monocytes and peritoneal fluid Mononuclear phagocytes in patients with endometriosis
2021-08-31 | GSE182983 | GEO
Project description:Purpose: This study was undertaken to evaluate the effect of peritoneal fluid from subjects with differing stages of endometriosis on gene expression in endometrial stromal cells. Methods: Peritoneal fluid from subjects with minimal, moderate, and severe stages of endometriosis or without endometriosis (controls) was collected, filtered and separated from peritoneal cells. Telomerase – immortalized human endometrial stromal cells (T-HESC) were treated with the peritoneal fluid samples for 48 hours. RNA was isolated from treated cells and processed for DNA microarray. Results: 162 genes were found to be differentially expressed in T-HESC cells treated with peritoneal fluid from subjects with differing stages of endometriosis. Three of the differentially expressed genes were chosen for confirmatory studies using quantitative RT-PCR; these were interleukin 8, corin and matrix metalloproteinase 3. The primary gene ontologies identified by microarray highlight functions expected to be involved in the establishment of endometriosis, such as proteases, signal transduction, defense and immune system, cell adhesion, cell cycle and cell death, cytoskeleton, transcriptional regulation and translation, extracellular matrix, and enzymes and metabolism. Conclusions: This study demonstrated that the severity of endometriosis affected the factors present in peritoneal fluid which, in turn, affected gene expression in endometrial stromal cells.
2019-07-01 | GSE101176 | GEO
Project description:The objective of the study was to compare the transcriptome of the primary eutopic and ectopic endometrial stromal cells isolated from paired eutopic endometrium and peritoneal lesions from women with endometriosis (N = 5) exposed to normoxic (20% O2) or hypoxic (1% O2) conditions for 48 hours. Induced expression of TGFBI was found in ectopic cells and ectopic & eutopic cells exposed to hypoxia at both RNA and protein (secreted to the culture media) levels. TGFBI gene and protein expression ex vivo in euoptic endometrium of women with endometriosis and controls (women without endometriosis) was found to be increased in the proliferative phase of menstrual cycle compared to secretory phase.
2024-12-07 | GSE269530 | GEO
Project description:Endometriosis -associated ovarian carcinoma (EAOC) is mostly malignant transformation from endometriomas. However, the endometriosis cancerogenesis remains to be established. Using spatial transcriptomic of human specimens of normal, endometriomas and EAOC, activation of Interleukin-17C (IL-17C) signaling is identified, with higher IL-17 receptor E (IL-17RE) expression in endometriotic cells, to be associated with cancerogenesis and which has no previous association with EAOC. Elevated IL-17C concentration is found in peritoneal fluid in women with ovarian cancer and IL-17RE-overexpressed endometriosis mice. In particular, IL-17C knockout reduces peritoneal fluid IL-17C concentration and inhibits ectopic lesion growth in endometriosis mice. Besides, the role of IL-17C in the endometriosis cancerogenesis was investigated by blocking the IL-17C/IL-17RE, modulating IL-17RE and neutralizing IL-17C in endometriotic cells, endometrial organoids and endometriosis mice. These data defined peritoneal fluid-mediated endometriosis cancerogenesis through IL-17C regulation and suggests that IL-17C/IL-17RE can thus potentially serve as novel targets for with high IL-17C.
2025-04-30 | GSE291389 | GEO