CD206+?macrophage is an accelerator of endometriotic-like lesion via promoting angiogenesis in the endometriosis mouse model.
Ontology highlight
ABSTRACT:
SUBMITTER: Ono Y
PROVIDER: S-EPMC7807007 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
CD206+ macrophage is an accelerator of endometriotic-like lesion via promoting angiogenesis in the endometriosis mouse model.
Ono Yosuke Y Yoshino Osamu O Hiraoka Takehiro T Sato Erina E Furue Akiko A Nawaz Allah A Hatta Hideki H Fukushi Yoshiyuki Y Wada Shinichiro S Tobe Kazuyuki K Hirota Yasushi Y Osuga Yutaka Y Unno Nobuya N Saito Shigeru S
Scientific reports 20210113 1
In endometriosis, M2 MΦs are dominant in endometriotic lesions, but the actual role of M2 MΦ is unclear. CD206 positive (+) MΦ is classified in one of M2 type MΦs and are known to produce cytokines and chemokines. In the present study, we used CD206 diphtheria toxin receptor mice, which enable to deplete CD206+ cells with diphtheria toxin (DT) in an endometriosis mouse model. The depletion of CD206+ MΦ decreased the total weight of endometriotic-like lesions significantly (p < 0.05). In the endo ...[more]
Similar Datasets
Project description:miRNA high-throughput sequencing was used to investigate endometriosis lesion-specific miRNA expression profiles by comparing a set of paired samples of peritoneal endometriotic lesions and matched healthy surrounding tissue together with eutopic endometrium of the same patients. We found that miRNAs of surrounding peritoneal tissue mask most of the miRNA expression differences that could originate from endometriotic tissue and thus only miRNAs with significantly different levels in the endometriotic lesions compared to peritoneal tissue were detected. According to the results of this study, two miRNAs – miR-34c and miR-449a showed remarkably higher expression in lesions compared to healthy tissue.
2015-01-06 | GSE56414 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) is a group of chronic interstitial pulmonary diseases characterized by myofibroblast proliferation and extracellular matrix deposition with limited treatment options. Based on our previous observation, we hypothesized microcystin-leucine arginine (LR), an environmental cyanobacterial toxin, could potentially suppress pulmonary fibrosis. In this study, we first demonstrated that chronic exposure of microcystin-LR by oral for weeks indeed attenuated the pulmonary fibrosis both on bleomycin-induced rat and fluorescein isothiocyanate-induced mouse models. Our data further indicated that treatment with microcystin-LR substantially reduced TGF-?1/Smad signaling in rat pulmonary tissues. The experiments in vitro found that microcystin-LR was capable of blocking epithelial-mesenchymal transition (EMT) and fibroblast-myofibroblast transition (FMT) through suppressing the differentiation of CD206+ macrophages. Mechanically, microcystin-LR was found to bind to glucose-regulated protein 78?kDa (GRP78) and suppress endoplasmic reticulum unfolded protein response (UPRER) signaling pathways. These events led to the modulation of M2 polarization of macrophages, which eventually contributed to the alleviation of pulmonary fibrosis. Our results revealed a novel mechanism that may account for therapeutic effect of microcystin-LR on IPF.
| S-EPMC7031231 | biostudies-literature
Project description:The pathophysiology of endometriosis remains unclear but involves a complex interaction between ectopic endometrium and host peritoneal tissues. We hypothesized that disruption of this interaction would suppress endometriotic lesion formation. We hoped to delineate the molecular and cellular dialogue between ectopic human endometrium and peritoneal tissues in nude mice as a first step toward testing this hypothesis. Human endometrium was xenografted into nude mice, and the resulting lesions were analyzed using microarrays. A novel technique was developed that unambiguously determined whether RNA transcripts identified via microarray analyses originated from human cells (endometrium) or mouse cells (mesothelium). Four key pathways (ubiquitin/proteasome, inflammation, tissue remodeling/repair, and ras-mediated oncogenesis) were revealed, demonstrating communication between host mesothelial cells and ectopic endometrium. Morphometric analysis of nude mouse lesions confirmed that necrosis, inflammation, healing and repair, and cell proliferation occurred during xenograft development. These processes were entirely consistent with the molecular networks revealed by the microarray data. The transcripts detected in the xenografts overlapped with differentially expressed transcripts in a comparison between paired eutopic and ectopic endometria from human endometriotic patients. For the first time, components of the interaction between ectopic endometrium and peritoneal stromal tissues are revealed. Targeted disruption of this dialogue is likely to inhibit endometriotic tissue formation and may prove to be an effective therapeutic strategy for endometriosis.
| S-EPMC2527068 | biostudies-literature
Project description:BACKGROUND:Endometriosis is a chronic, painful, and inflammatory disease characterized by extra-uterine growth of endometrial tissues. Increased angiogenesis and resistance to apoptosis have been suggested to be involved in pathogenesis and development of endometriosis. The objective of this study was to examine apoptosis potential and angiogenesis contribution of eutopic (EuESCs) and ectopic (EESCs) endometrial stromal cells in patients with endometriosis compared to endometrial stromal cells from non-endometriotic controls (CESCs). METHODS:Stromal cells were isolated by enzymatic digestion of ectopic (n = 11) and eutopic (n = 17) endometrial tissues from laparoscopically-confirmed endometriotic patients. Endometrial stromal cells of 15 non-endometriotic patients served as control. Following cell characterization by immunofluorescent staining and flow cytometry using a panel of antibodies, the total RNA was isolated from the cultured cells, and analyzed for the expression of genes involved in apoptosis (Bcl-2, Bcl-xL, Bax, and caspase-3) and angiogenesis [vascular endothelial growth factor-A (VEGF-A) and hepatocyte growth factor (HGF)] by Real-time PCR. RESULTS:Significantly higher gene expression levels of Bcl-2 and Bcl-xL were found in EESCs compared with EuESCs and CESCs (p < 0.01). The gene expression of Bax in EESCs, EuESCs, and CESCs was not statistically significant. Furthermore, EuESCs exhibited a significantly lower caspase-3 gene expression compared with CESCs (p < 0.01) or EESCs (p < 0.05). Regarding angiogenesis, VEGF-A gene expression in EESCs (p < 0.001) and EuESCs (p < 0.05) were significantly higher compared with those of CESCs. EESCs exhibited a significantly higher HGF gene expression compared with EuESCs (p < 0.05). CONCLUSIONS:These findings suggest reduced propensity to apoptosis and increased angiogenesis potential of EESCs, which may be involved in pathogenesis of endometriosis.
| S-EPMC6945780 | biostudies-literature
Project description:The development and progression of endometriotic lesions are poorly understood, but immune cell dysfunction and inflammation are closely associated with the pathophysiology of endometriosis. A lack of suitable 3D in vitro models permitting the study of interactions between cell types and the microenvironment is a contributing factor. To address this limitation, we developed endometriotic organoids (EO) to explore the role of epithelial-stromal interactions and model peritoneal cell invasion associated with lesion development. Using a non-adherent microwell culture system, spherical organoids were generated with endometriotic epithelial cells (12Z) combined with immortalized endometriotic stromal cells (iEc-ESC) or immortalized uterine stromal cells (iHUF). Organoids self-organized with stromal cells occupying the center and epithelial cells on the periphery of the organoid. Endometriotic organoids (EO), containing iEc-ESC, resulted in the development of stratified 12Z epithelial cells compared to those with iHUF where the 12Z cells developed as a single layered epithelium. Transcriptomic analysis found 4,522 differentially expressed genes (DEG) between EO and 12Z/iHUF organoids, and the top DEG included increased expression of interleukins and prostaglandin synthase enzymes. An overlap of the EO DEG with baboon endometriotic lesions was highly significant. Finally, to mimic invasion of endometrial tissue into the peritoneum, a model was developed using EO and extracellular matrix containing human peritoneal mesothelial cells (LP9). Invasion of EO into the extracellular matrix-LP9 layer was increased in presence of estrogen or THP1-derived proinflammatory macrophages. Taken together, our results strongly support the concept that EO are an appropriate model for dissecting mechanisms that contribute to endometriotic lesion development.
2022-06-15 | GSE202661 | GEO
Project description:Endometriosis, defined as growth of the endometrial cells outside the uterus, is an inflammatory disorder that is associated with chronic pelvic pain and infertility in women of childbearing age. Although the estrogen-dependence of endometriosis is well known, the role of progesterone in development of this disease remains poorly understood. In this study, we developed a disease model in which endometriosis was induced in the peritoneal cavities of immunocompetent female mice, and maintained with exogenous estrogen. The endometriosis-like lesions that were identified at a variety of ectopic locations exhibited abundant blood supply and extensive adhesions. Histological examination revealed that these lesions had a well-organized endometrial architecture and fibrotic response, resembling those recovered from clinical patients. In addition, an extensive proliferation, inflammatory response, and loss of estrogen receptor alpha (ERα) and progesterone receptor (PR) expression were also observed in these lesions. Interestingly, administration of progesterone before, but not after, lesion induction suppressed lesion expansion and maintained ERα and PR expressions. These progesterone-pretreated lesions exhibited attenuation in KI67, CD31, and pro-inflammatory cytokine expression as well as macrophage infiltration, indicating that progesterone ameliorates endometriosis progression by inhibiting cell proliferation, inflammation and neovascularization. Our studies further showed that suppression of global DNA methylation by application of DNA methyltransferase inhibitor to female mice bearing ectopic lesions restrained lesion expansion and restored ERα and PR expression in eutopic endometrium and ectopic lesions. These results indicate that epigenetic regulation of target gene expression via DNA methylation contributes, at least in part, to progesterone resistance in endometriosis.
| S-EPMC5077092 | biostudies-literature
Project description:Endometriosis is a benign disease affecting one in ten women of reproductive age worldwide. Although the pain level is not correlated to the extent of the disease, it is still one of the cardinal symptoms strongly affecting the patients' quality of life. Yet, a molecular mechanism of this pathology, including the formation of pain, remains to be defined. Recent studies have indicated a close interaction between newly generated nerve cells and macrophages, leading to neurogenic inflammation in the pelvic area. In this context, the responsiveness of an endometriotic cell culture model was characterized upon inflammatory stimulation by employing a multi-omics approach, including proteomics, metabolomics and eicosanoid analysis. Differential proteomic profiling of the 12-Z endometriotic cell line treated with TNFα and IL1β unexpectedly showed that the inflammatory stimulation was able to induce a protein signature associated with neuroangiogenesis, specifically including neuropilins (NRP1/2). Untargeted metabolomic profiling in the same setup further revealed that the endometriotic cells were capable of the autonomous production of 7,8-dihydrobiopterin (BH2), 7,8-dihydroneopterin, normetanephrine and epinephrine. These metabolites are related to the development of neuropathic pain and the former three were found up-regulated upon inflammatory stimulation. Additionally, 12-Z cells were found to secrete the mono-oxygenated oxylipin 16-HETE, a known inhibitor of neutrophil aggregation and adhesion. Thus, inflammatory stimulation of endometriotic 12-Z cells led to specific protein and metabolite expression changes suggesting a direct involvement of these epithelial-like cells in endometriosis pain development.
| S-EPMC8393596 | biostudies-literature
Project description:Endometriosis occurs when endometrial-like tissue grows outside the uterine cavity, leading to pelvic pain, infertility, and increased risk of ovarian cancer. The present study describes the optimization and characterization of cellular spheroids as building blocks for Kenzan scaffold-free method biofabrication and proof-of-concept models of endometriosis and the endometriotic microenvironment. The spheroid building blocks must be of a specific diameter (~500 ?m), compact, round, and smooth to withstand Kenzan biofabrication. Under optimized spheroid conditions for biofabrication, the endometriotic epithelial-like cell line, 12Z, expressed high levels of estrogen-related genes and secreted high amounts of endometriotic inflammatory factors that were independent of TNF? stimulation. Heterotypic spheroids, composed of 12Z and T-HESC, an immortalized endometrial stromal cell line, self-assembled into a biologically relevant pattern, consisting of epithelial cells on the outside of the spheroids and stromal cells in the core. 12Z spheroids were biofabricated into large three-dimensional constructs alone, with HEYA8 spheroids, or as heterotypic spheroids with T-HESC. These three-dimensional biofabricated constructs containing multiple monotypic or heterotypic spheroids represent the first scaffold-free biofabricated in vitro models of endometriosis and the endometriotic microenvironment. These efficient and innovative models will allow us to study the complex interactions of multiple cell types within a biologically relevant microenvironment.
| S-EPMC7700676 | biostudies-literature
Project description:Gene expression profiling of primary stromal cell cultures isolated from human endometrium and ovarian endometriosis. Samples are derived from the endometrium of 6 healthy patients and the endometriomas of 6 diseased patients. The results indicate the gene expression differences between these two cell populations. Stromal cells were obtained from human normal endometrial tissues and ovarian endometriomas. The tissues were digested enzymatically, and pure stromal cell populations were established.
2014-08-01 | E-GEOD-58178 | biostudies-arrayexpress
Project description:Endometriosis results from ectopic invasion of endometrial tissue within the peritoneal cavity. Aberrant levels of the estrogen receptor (ER), ER? and ER?, and higher incidence of autoimmune disorders are observed in women with endometriosis. An immunocompetent mouse model of endometriosis was used in which minced uterine tissue from a donor was dispersed into the peritoneal cavity of a recipient. Wild-type (WT), ER?-knockout (?ERKO), and ?ERKO mice were donors or recipients to investigate the roles of ER?, ER?, and estradiol-mediated signaling on endometriosis-like disease. Mice were treated with vehicle or estradiol, and resulting location, number, and size of endometriosis-like lesions were assessed. In comparison with WT lesions in WT hosts, ?ERKO lesions in WT hosts were smaller and fewer in number. The effect of ER status and estradiol treatment on nuclear receptor status, proliferation, organization, and inflammation within lesions were examined. ?ERKO lesions in WT hosts did not form distal to the incision site, respond to estradiol, or proliferate but did have increased inflammation. WT lesions in ?ERKO hosts did respond to estradiol, proliferate, and show decreased inflammation with treatment, but surprisingly, progesterone receptor expression and localization remained unchanged. Only minor differences were observed between WT lesions in ?ERKO hosts and ?ERKO lesions in WT hosts, demonstrating the estradiol-mediated signaling responses are predominately through ER?. In sum, these results suggest ER in both endometriosis-like lesions and their environment influence lesion characteristics, and understanding these interactions may play a critical role in elucidating this enigmatic disease.
| S-EPMC3404357 | biostudies-literature