Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Maresin 1 Repletion Improves Muscle Regeneration After Volumetric Muscle Loss

ABSTRACT: The acute traumatic or surgical loss of skeletal muscle, known as volumetric muscle loss (VML), is a devastating type of injury that results in exacerbated and persistent inflammation followed by fibrosis. The mechanisms that mediate the magnitude and duration of the inflammatory response and ensuing fibrosis after VML remain understudied, and as such, the development of regenerative therapies has been limited. To address this need, we profiled how lipid mediators, which are potent regulators of the immune response after injury, varied with VML injuries that heal or result in fibrosis. We observed that non-healing VML injuries displayed increased pro-inflammatory eicosanoids and a lack of pro-resolving lipid mediators. Treatment of VML with a pro-resolving lipid mediator synthesized from docosahexaenoic acid, called Maresin 1, ameliorated fibrosis through reduction of neutrophils and macrophages and enhanced recovery of muscle strength. These results expand our knowledge of the dysregulated immune response that develops after VML and identify a novel immuno-regenerative therapeutic modality in Maresin 1.

ORGANISM(S): Mus musculus

PROVIDER: GSE215808 | GEO | 2024/01/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Single cell deconstruction of murine volumetric muscle loss reveals inflammatory imbalances preventing muscle stem cell mediated regeneration

Project description:Volumetric muscle loss (VML) overwhelms the innate regenerative capacity of mammalian skeletal muscle (SkM), leading to numerous disabilities and reduced quality of life. Immune cells are critical responders to muscle injury and guide tissue resident stem cell and progenitor mediated myogenic repair. However, how immune cell infiltration and inter-cellular communication networks are altered following VML and drive pathological outcomes remains under-explored. Herein, we characterize the cellular and molecular mechanisms of VML injuries that result in fibrotic degeneration or regeneration of SkM. Following degenerative VML injuries, we observe heightened infiltration of a previously uncharacterized population of Natural Killer (NK) cells as well as persistence of neutrophils beyond two weeks post injury. Functional validation of NK cells revealed an antagonistic role on neutrophil accumulation in part via CCR1 mediated chemotaxis. The persistent infiltration of neutrophils in degenerative VML injuries was found to contribute to impairments in muscle stem cell regenerative function, which was also attenuated by transforming growth factor beta 1 (TGFb1). Blocking TGFb signaling antagonized neutrophil accumulation, reduced fibrosis, and improved muscle specific force. Collectively, these results enhance our understanding of immune cell-stem cell crosstalk that drives regenerative dysfunction and provide further insight into possible avenues for fibrotic therapy exploration.

2022-04-04 | GSE163376 | GEO

Maresin-1 and Resolvin E1 promote regenerative properties of periodontal ligament stem cells under inflammatory conditions

Project description:Maresin-1 (MaR1) and Resolvin E1 (RvE1) are specialized pro-resolving lipid mediators (SPMs) that regulate inflammatory processes. We have previously demonstrated the hard and soft tissue regenerative capacity of RvE1 in an in vivo model of periodontal disease characterized by inflammatory tissue destruction. Regeneration of periodontal tissues requires a well-orchestrated processes mediated by periodontal ligament stem-cells. However, limited data are available on how SPMs can regulate the regenerative properties of human periodontal ligament stem cells (hPDLSCs) under inflammatory conditions. Thus, we measured the impact of MaR1 and RvE1 in an in vitro model of hPDLSCs after stimulation with IL-1β and TNF-α by evaluating pluripotency, migration, proliferation, cell death, periodontal ligament markers (α-smooth muscle actin, tenomodulin, and periostin), cementum-osteogenic differentiation and phosphoproteomic perturbations. The data showed that the inflammatory milieu suppresses pluripotency, proliferation and migration of hPDLSCs; MaR1 and RvE1 both restored regenerative capacity by increasing hPDLSC proliferation, accelerating wound healing/migration, and upregulating periodontal ligament markers and cementum-osteogenic differentiation. Protein phosphorylation perturbations were associated with the SPM-induced regenerative capacity of hPDLSCs. Together, these results demonstrate that MaR1 and RvE1 restore or improve the regenerative properties of highly specialized stem cells when inflammation is present and offer opportunities for direct pharmacologic treatment of lost tissue integrity.

2021-09-09 | PXD019546 | Pride

Deconstruction of cellular dynamics after treatment of volumetric muscle loss injury with extracellular matrix

Project description:Volumetric muscle loss (VML) is an acute loss of a critical volume of skeletal muscle that results in inflammation, fibrotic scarring in muscle tissue, and permanent muscle defects. The cellular and molecular processes that underlie fibrosis induced from VML injury need to be evaluated in larger animal models. Therefore, we used a canine model of VML alongisde treatment with an extracellular matrix (ECM) hydrogel. Treatment with the ECM hydrogel improved muscle regenerative responses and decreased proportions and spatial signatures of fibrotic and inflammatory cell populations.

2024-06-01 | GSE266585 | GEO

Spatiotemporal mapping of immune and stem cell dysregulation after volumetric muscle loss

Project description:Volumetric muscle loss (VML) is an acute trauma that results in persistent inflammation, supplantation of muscle tissue with fibrotic scarring, and decreased muscle function. The cell types, nature of cellular communication, and tissue locations that drive the aberrant VML response have remained elusive. Herein, we used spatial transcriptomics on mouse and canine models of VML and observed VML engenders a unique spatial pro-fibrotic pattern driven by crosstalk between fibrotic and inflammatory macrophages and mesenchymal derived cells. The dysregulated response was conserved between murine and canine VML models, albeit with varying kinetics, and impinged on muscle stem cell mediated repair. Targeting this circuit in a murine model resulted in increased regeneration and reductions in inflammation and fibrosis. Collectively, these results enhance our understanding of the cellular crosstalk that drives aberrant regeneration and provides further insight into possible avenues for fibrotic therapy exploration.

2023-02-23 | GSE205707 | GEO

MCTR3 reprograms arthritic monocytes to upregulate Arginase-1 and exert pro-resolving and tissue-protective functions in experimental arthritis

Project description:We aim to demonstrate that pro-resolving mediator maresin conjugate in tissue regeneration 3 (MCTR3) potently regulates join arthritic inflammation as well as bone and cartilage repair.

2022-03-31 | GSE174118 | GEO

Multiscale analysis of a regenerative therapy for treatment of volumetric muscle loss injury

Project description:Skeletal muscle possesses a remarkable capacity to regenerate when injured, but when confronted with major traumatic injury resulting in volumetric muscle loss (VML), the regenerative process consistently fails. The loss of muscle tissue and function from VML injury has prompted development of a suite of therapeutic approaches but these strategies have proceeded without a comprehensive understanding of the molecular landscape that drives the injury response. Herein, we administered a VML injury in an established rodent model and monitored the evolution of the healing phenomenology over multiple time points using muscle function testing, histology, and expression profiling by RNA sequencing. The injury response was then compared to a regenerative medicine treatment using orthotopic transplantation of autologous minced muscle grafts (~1 mm3 tissue fragments). A chronic inflammatory and fibrotic response was observed at all time points following VML. These results suggest that the pathological response to VML injury during the acute stage of the healing response overwhelms endogenous and therapeutic regenerative processes. Overall, the data presented delineate key molecular characteristics of the pathobiological response to VML injury that are critical effectors of effective regenerative treatment paradigms.

2018-05-23 | GSE114799 | GEO

Maresin 1 attenuates neuroinflammation in a mouse model of perioperative neurocognitive disorders

Project description:Maresin 1 administered to mice prior to orthopedic surgery exerts distinct anti-inflammatory and pro-resolving effects through regulation of MΦ infiltration, NF-κB signaling, and cytokine release. We used microarrays to detail the global programme of gene expression underlying Maresin 1 effect on mouse hippocampus and identified distinct classes of dysregulated genes during this process.

2018-11-13 | GSE115440 | GEO

Local IL-10 delivery modulates the immune response and enhances repair of volumetric muscle loss muscle injury

Project description:To explore the impact of targeting IL-10 signaling, tibialis anterior (TA) VML injuries were created and then treated in Sprague Dawley rats using an autologous minced muscle regenerative medicine repair strategy in combination with delayed exogenous IL-10 delivery. We then performed gene expression profiling analysis using data obtained from RNA-seq from rat muscles (n=4 for IL-10 treatment, n=4 for PBS control , and n=4 for uninjured control) at day 14 post injury

2022-06-26 | GSE206823 | GEO

Specialized Pro-resolving Mediators Regulate Treg Differentiation

Project description:Specialized Pro-resolving Mediators Regulate Treg Differentiation

| PRJNA590755 | ENA

Chronic Stress Alters Lipid Mediator Profiles Associated with Immune-Related Gene Expressions in Mouse Bone Marrow and Spleen

Project description:Despite the importance of lipid mediators in stress and depression and their link to inflammation, the influence of stress on these mediators and their role in inflammation is not fully understood. This study used RNA-seq, LC-MS/MS, and flow cytometry analyses in a mouse model subjected to chronic social defeat stress to explore the effects of acute and chronic stress on lipid mediators, gene expression, and cell population in the bone marrow and spleen. We observed that chronic stress in the bone marrow precipitated a persistent lymphoid-to-myeloid transition, accompanied by corresponding gene expression changes. This change was associated with decreased levels of 15-deoxy-d12,14-prostaglandin J2, a lipid mediator that inhibits inflammation. Conversely, in the spleen, chronic stress led to a transient lymphoid-to-myeloid transition, alongside gene expression patterns suggestive of extramedullary hematopoiesis. These changes were linked to lower levels of 12-HEPE and resolvins, both critical for inhibiting and resolving inflammation. Our findings highlight the significant role of anti-inflammatory and pro-resolving lipid mediators in the immune responses induced by chronic stress in the bone marrow and spleen. This study paves the way for understanding how these lipid mediators contribute to the immune mechanisms of stress and depression.

2024-02-14 | GSE254978 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data