Similar Datasets
Project description:Immunoresolving lipid mediators support effective skeletal muscle repair
| PRJNA611966 | ENA
Project description:We employed RNA-sequencing with surgically resected planaria and cysteinyl-specialized pro-resolving mediators (cys-SPMs), including MCTR3, PCTR3 and RCTR3 to identify genes and pathways activated by cys-SPMs.
2021-03-01 | GSE160278 | GEO
Project description:The intrinsic connection between inflammation and tumor promotion is well characterized and is a key pathogenic event in patients with colorectal cancer (CRC), the second most common cause of tumor-related death in western countries. Environmental factors and chronic inflammation represent the major causes of intestinal carcinogenesis. In fact, patients suffering from inflammatory bowel diseases, including Crohn’s disease and Ulcerative Colitis (UC), have high risk of developing colitis-associated CRC with poor prognoses. Therefore, targeting the cancer-associated inflammation may offer new avenues for cancer treatment. In fact, several anti-inflammatory drugs, have been used for prophylaxis and have shown efficacy in contrasting cancer, despite various adverse side effects. Thus, there is an urgent need to discover novel cancer-associated mechanisms to develop alternative therapies that may reduce aberrant inflammatory responses without interfering with physiological defenses against infection and functional anti-tumor immunity. A novel approach promoting anti-tumor immunity has been recently proposed after the discovery of potent, endogenous, specialized pro-resolving mediators (SPMs), including lipoxins, resolvins, protectins, and maresins, mainly derived from omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) via COX, LOX and CYP450 pathways, mediated by MFSD2A. Due to the potent bioactivity of SPMs in resolving inflammation and because of the correlation between inflammation and cancer, the roles of these lipid mediators have attracted great attention for their potential therapeutic role in cancer treatment, including CRC. Nevertheless, the understanding of the endogenous mechanisms that limit the inflammatory response during CRC development is incomplete and requires further investigation.
Based on the preliminary results indicating that dysfunctional MFSD2A-dependent pro-resolving pathways may foster CRC development, the investigators aim to define the functional role of MFSD2A in orchestrating pro-resolving pathways in the intestinal endothelium of metastatic and not metastatic CRC patients.
This is a cross-sectional single-center observational study involving patients with CRC. The investigators will enroll 15 patients with colorectal cancer (CRC) stratified by tumor stage (T0 / T1-T4, M0 / M1, N0 / N1 / N2) undergoing surgery in the Gastroenterology and Digestive Endoscopy unit within Gastro Center (IRCCS Ospedale San Raffaele).
Human Intestinal Microvascular Endothelial Cells (HIMEC) will be generated from each sample of cancer surgical specimens, while the healthy cells will be derived from the healthy margins of the colorectal resection of the same CRC patients.
MFSD2A will be overexpressed or silenced and the investigators will evaluate its biological effects in both tumor-derived HIMECs and healthy tissue-derived HIMECs through transcriptomics and lipidomics analysis. The investigators will also exploit a possible novel therapy based on the delivery of MFSD2A encoding plasmid-conjugated liposomes.
| 108244 | ecrin-mdr-crc
Project description:Secondary progressive multiple sclerosis (SPMS) most challenging aspect is the lack of efficient regenerative response for remyelination, which is carried out by the endogenous population of adult oligoprogenitor cells (OPCs) after proper activation. OPCs must proliferate and migrate to the lesion and then differentiate into mature oligodendrocytes. To investigate the OPC cellular component in SPMS we developed iPSCs from SPMS affected donors and age matched controls (CT). We confirmed their efficient and similar OPC differentiation capacity, although we reported SPMS-OPCs are transcriptional distinguishable from their CT counterparts. Analysis of OPC-generated conditioned media (CM) also evidenced differences in protein secretion. We further confirmed SPMS-OPC CM presents a deficient capacity to stimulate OPC in vitro migration that can be compensated by exogenous addition of specific components. Our results provide an SPMS-OPC cellular model and encouraging venues to study potential cell communication deficiencies in the progressive form of MS for future treatment strategies.
2020-07-30 | GSE151306 | GEO
Project description:Time-dependent profiles were recapitulated in sorted neutrophils and Ly6Chigh and Ly6Clow muscle macrophages, with a distinct pro-resolving signature observed in Ly6Clow reparative macrophages. RNA-seq analysis of macrophages stimulated with resolvin D2 (RvD2) showed similarities to transcriptional changes found during the temporal Ly6Chigh to Ly6Clow phenotypic transition. Importantly, RvD2 promoted the temporal progression from Ly6Chigh to Ly6Clow macrophages in vivo.
2019-02-01 | GSE114291 | GEO
Project description:IntroductionMesenchymal stem and progenitor cells (MSCs), which normally reside in the bone marrow, are critical to bone health and can be recruited to sites of traumatic bone injury, contributing to new bone formation. The ability to control the trafficking of MSCs provides therapeutic potential for improving traumatic bone healing and therapy for genetic bone diseases such as hypophosphatasia.MethodsIn this study, we explored the sphingosine-1-phosphate (S1P) signaling axis as a means to control the mobilization of MSCs into blood and possibly to recruit MSCs enhancing bone growth.ResultsLoss of S1P receptor 3 (S1PR3) leads to an increase in circulating CD45-/CD29+/CD90+/Sca1 putative mesenchymal progenitor cells, suggesting that blocking S1PR3 may stimulate MSCs to leave the bone marrow. Antagonism of S1PR3 with the small molecule VPC01091 stimulated acute migration of CD45-/CD29+/CD90+/Sca1+ MSCs into the blood as early as 1.5 hours after treatment. VPC01091 administration also increased ectopic bone formation induced by BMP-2 and significantly increased new bone formation in critically sized rat cranial defects, suggesting that mobilized MSCs may home to injuries to contribute to healing. We also explored the possibility of combining S1P manipulation of endogenous host cell occupancy with exogenous MSC transplantation for potential use in combination therapies. Importantly, reducing niche occupancy of host MSCs with VPC01091 does not impede engraftment of exogenous MSCs.ConclusionsOur studies suggest that MSC mobilization through S1PR3 antagonism is a promising strategy for endogenous tissue engineering and improving MSC delivery to treat bone diseases.
| S-EPMC6029871 | biostudies-literature
Project description:Muscle damage elicits a sterile immune response that facilitates complete regeneration. Here, we used mass spectrometry-based lipidomics to map the mediator lipidome during the transition from inflammation to resolution and regeneration in skeletal muscle injury. We observed temporal regulation of glycerophospholipids and production of pro-inflammatory lipid mediators (for example, leukotrienes and prostaglandins) and specialized pro-resolving lipid mediators (for example, resolvins and lipoxins) that were modulated by ibuprofen. These time-dependent profiles were recapitulated in sorted neutrophils and Ly6Chi and Ly6Clo muscle-infiltrating macrophages, with a distinct pro-resolving signature observed in Ly6Clo macrophages. RNA sequencing of macrophages stimulated with resolvin D2 showed similarities to transcriptional changes found during the temporal transition from Ly6Chi macrophage to Ly6Clo macrophage. In vivo, resolvin D2 increased Ly6Clo macrophages and functional improvement of the regenerating muscle. These results reveal dynamic lipid mediator signatures of innate immune cells and provide a proof of concept for their exploitable effector roles in muscle regeneration.
| S-EPMC6537107 | biostudies-literature
Project description:We aim to demonstrate a central role for omega-3 derived autacoids, termed specialized pro-resolving mediators (SPM), in the differentiation and maturation of Tregs.
2021-06-10 | GSE140750 | GEO
Project description:Inflammation is the natural defensive response of the immune system to an injury or infection and is regulated by small molecule mediators triggering different phases of the inflammatory process. In particular, lipid mediators (LM) and cytokines exhibit crucial regulatory functions in the progression and resolution of inflammation. Macrophages play a central role in this process and can adopt distinct phenotypes with specialized functions depending on their microenvironment: inflammatory M1 macrophages drive inflammation by the release of pro-inflammatory cytokines and LMs, like prostaglandins (PG) and leukotrienes (LT), while resolving M2 macrophages promote inflammation resolution and tissue regeneration by production of anti-inflammatory cytokines and specialized pro resolving mediators (SPM). Aging is associated with chronic and unresolved, low-grade inflammation (“inflammaging”) and aging-related dysfunction of macrophages in the resolution of inflammation and tissue maintenance has been reported. Yet, the underlying molecular mechanisms and functional consequences of latter processes remain poorly understood. Here, we show that polarization of peritoneal macrophages (PM) from geriatric mice towards an M2-like phenotype is impaired versus adult mice, resulting in aberrant LM formation and cytokine release. In PMs isolated from adult mice (PM-A) we observed a shift in LM formation from PGs and LTs to SPMs already after 4 h of polarization towards M2 with interleukin (IL) 4. In contrast, PMs from geriatric mice (PM-G) produced mainly LTs and PGs upon polarization. This pattern persists over the course of 48 h of polarization. Proteomic profiling revealed that polarization of PM A towards M2 yields a more distinct phenotype, clearly separated from M1, when compared to PM-G. We observed similar aging-related changes in the lipidome and cytokine profile of spleen, lung and liver tissue from mice. Hence, we hypothesize that during aging macrophage polarization towards M2 is impaired, which in turn drives chronic inflammation and disturbs tissue maintenance. By combining state-of-the art lipidomic and proteomic profiling we aim to uncover new molecular targets for pharmaceutical interventions to improve therapeutic strategies for elderly patients with chronic inflammatory diseases.
2023-10-24 | PXD027357 | Pride
Project description:Specialized Pro-resolving Mediators Regulate Treg Differentiation
| PRJNA590755 | ENA