Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Peripheral Nerve Block with Ropivacaine Ameliorates Acute Compartment Syndrome by Promoting Macrophage M2 Polarization via JAK-STAT Signaling

ABSTRACT: This work constructed a rat acute compartment syndrome (ACS) model to investigate the protective effect of ropivacaine peripheral nerve block (PNB) and its molecular mechanism. In vivo experiments showed that combined sciatic and femoral nerve block achieved the best therapeutic effect, alleviating tissue inflammatory injury and improving histopathological and limb function. In LPS-induced RAW264.7 macrophages, ropivacaine induced M2 macrophage polarization, inhibited pro-inflammatory cytokine secretion and cell migration without cell toxicity. Transcriptome sequencing screened out the JAK-STAT signaling pathway as the key enriched pathway. Further verification confirmed that ropivacaine activated JAK2-STAT3 signaling. Blocking JAK2 with inhibitor AG490 abolished M2 polarization and anti-inflammatory effects both in vitro and in vivo, and eliminated the tissue protection of PNB in ACS model animals. Our findings demonstrate that ropivacaine PNB relieves acute compartment syndrome inflammation by facilitating M2 macrophage polarization via the JAK-STAT pathway, providing a new non-surgical intervention strategy for ACS treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE336799 | GEO | 2026/09/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression profiling of primary leukemia initiating cell-enriched population induced by AML1-ETO9a

Project description:Combined gene expression and DNA occupancy profiling identifies JAK/STAT signaling as a valid therapeutic target of t(8;21) AML t(8;21) is commonly associated with acute myeloid leukemia (AML). The resulting AML1-ETO fusion proteins are involved in the pathogenesis of AML. To identify novel molecular and therapeutic targets, we performed combined gene expression and promoter occupancy profiling using a primary leukemia initiating cell-enriched population induced by AML1-ETO9a (AE9a). CD45, a negative regulator of cytokine/growth factor receptor and JAK/STAT signaling, is greatly downregulated; furthermore JAK1 and JAK2 are upregulated in these leukemia cells. Consequently, JAK/STAT signaling is enhanced in the AE9a leukemia cells. Importantly, AE9a leukemia cells are highly susceptible to perturbation of JAK/STAT signaling, and a JAK2-selective inhibitor, TG101209, effectively targets these leukemia cells in vivo, suggesting the potential efficacy of JAK2 inhibitors in treating t(8;21) AML. Wild-type or AE9a leukemic samples in triplicate.

2012-09-04 | E-GEOD-15195 | biostudies-arrayexpress

Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis [HEL cell lines]

Project description:We used expression profiling, SNP arrays, and mutational profiling to investigate a well-characterized cohort of MPN patients. MPN patients with homozygous JAK2V617F mutations were characterized by a distinctive transcriptional profile. Notably, a transcriptional signature consistent with activated JAK2 signaling is seen in all MPN patients regardless of clinical phenotype or mutational status. In addition, the activated JAK2 signature was present in patients with somatic CALR mutations. Conversely, we identified a gene expression signature of CALR mutations; this signature was significantly enriched in JAK2-mutant MPN patients consistent with a shared mechanism of transformation by JAK2 and CALR mutations. We also identified a transcriptional signature of TET2 mutations in MPN patent samples. Our data indicate that MPN patients, regardless of diagnosis or JAK mutational status are characterized by a distinct gene expression signature with upregulation of JAK-STAT target genes, demonstrating the central importance of the JAK-STAT pathway in MPN pathogenesis. [HEL cell lines] We have performed gene expression profiling in the JAK2V617F homozygous mutant HEL cell line following treatment with 2 independent shRNAs targeting JAK2 or 2 different control shRNAs

2014-06-03 | E-GEOD-54645 | biostudies-arrayexpress

Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis [MPN patients]

Project description:We used expression profiling, SNP arrays, and mutational profiling to investigate a well-characterized cohort of MPN patients. MPN patients with homozygous JAK2V617F mutations were characterized by a distinctive transcriptional profile. Notably, a transcriptional signature consistent with activated JAK2 signaling is seen in all MPN patients regardless of clinical phenotype or mutational status. In addition, the activated JAK2 signature was present in patients with somatic CALR mutations. Conversely, we identified a gene expression signature of CALR mutations; this signature was significantly enriched in JAK2-mutant MPN patients consistent with a shared mechanism of transformation by JAK2 and CALR mutations. We also identified a transcriptional signature of TET2 mutations in MPN patent samples. Our data indicate that MPN patients, regardless of diagnosis or JAK mutational status are characterized by a distinct gene expression signature with upregulation of JAK-STAT target genes, demonstrating the central importance of the JAK-STAT pathway in MPN pathogenesis. [MPN patients] We have performed microarray gene expression analysis in 93 patients with MPNs (28 PV, 47 ET, 18 MF) and 11 age-matched normal donors.

2014-06-03 | E-GEOD-54644 | biostudies-arrayexpress

Expression profiling of primary leukemia initiating cell-enriched population induced by AML1-ETO9a

2012-09-04 | GSE15195 | GEO

Effect of a JAK inhibitor on gene expression of HUT78 cell line

Project description:Developing targeted therapy for cutaneous T cell lymphoma (CTCL) patients still requires actionable mutated genes and deregulated pathways to be identified. There is increasing evidence that activating mutations in JAK genes and deregulated JAK/STAT signaling are important mechanisms involved in multiple B and T cell malignancies, including CTCL. Therefore, in this study we focused on studying the mutational status of JAK1, JAK2 and JAK3 genes in a series of human CTCL lesions and cell lines using next-generation sequencing (NGS). We found that 7 of 48 (14.7%) of the analyzed cases harbored mutations in the JAK1 and JAK3 genes that mainly affected the pseudokinase domain of the corresponding proteins. On the basis of these results, we used a specific JAK inhibitor (INCB018424) in a series of CTCL cell lines with deregulated JAK/STAT activity. Treatment of CTCL cells with INCB018424 resulted in dose-dependent reduction of activated STAT expression, diminished cell viability, and increased apoptosis. We also studied global changes in gene expression in cells with mutated JAK1 and JAK3 proteins treated with INCB018424 and identified multiple genes that were differentially regulated by JAK/STAT signaling, such as FGF20 (upregulated) and EGR1 (downregulated). Thus, our results show that the detection of deregulated JAK/STAT signaling in CTCL lesions via JAK mutations or other surrogate markers may serve to indicate the clinical use of JAK/STAT inhibitors. 3 replicates of cells treated with DMSO or JAKi during 30 min and 3h

2015-10-31 | E-GEOD-68562 | biostudies-arrayexpress

Genomic profiling of neoplasms developed in SEC31A-JAK2 expressing mice

Project description:The genetics of classical Hodgkin lymphoma (cHL) is poorly understood. The finding of a JAK2-involving t(4;9)(q21;p24) in one case of cHL prompted us to characterize this translocation on a molecular level and to determine the prevalence of JAK2 rearrangements in cHL. We showed that the t(4;9)(q21;p24) leads to a novel SEC31A-JAK2 fusion. Screening of 131 cHL cases identified one additional case with SEC31A-JAK2 and two additional cases with rearrangements involving JAK2. We demonstrated that SEC31A-JAK2 is oncogenic in vitro and acts as a constitutively activated tyrosine kinase that is sensitive to JAK inhibitors. In vivo, SEC31A-JAK2 was found to induce a T-lymphoblastic lymphoma or myeloid hyperplasia in a murine bone marrow transplant model. Altogether, we identified SEC31A-JAK2 as a first aberration characteristic for cHL and provide evidence that JAK2 rearrangements occur in a minority of cHL cases. Given the proven oncogenic potential of this novel fusion, our studies provide new insights into the pathogenesis of cHL and indicate that in at least some cases, constitutive activation of the JAK-STAT pathway is caused by JAK2 rearrangements. The finding that SEC31A-JAK2 responds to JAK inhibitors indicates that patients with cHL and JAK2 rearrangements may benefit from targeted therapies. Genomic profiling of primary and secondary transplanted mice expressing SEC31A-JAK2 with myeloid hyperplasia and T-lymphoblastic lymphoma Individual sample against a normal control

2010-07-08 | E-GEOD-22404 | biostudies-arrayexpress

In situ piezoelectricity induces M2 polarization of macrophages to regulate Schwann cells for alleviating neuropathic pain of CCI rats

Project description:Peripheral nerve injuries often lead to neuropathic pain (NP), which is influenced by macrophage polarization, impacting Schwann cell function. Bioelectric signals, particularly from piezoelectric materials like polyvinylidene fluoride (PVDF), play a pivotal role in modulating macrophage polarization. In this study, we demonstrate that PVDF's piezoelectric properties enhance M2 polarization during hypoxia macrophage model, as indicated by increased CD206 (M2 marker) expression and decreased CD8 (M1 marker). This shift in polarization is linked to enhanced secretion of Arg-1 and IL-10 from M2 macrophages, and reduced levels of ROS, iNOS, and TNF-α from M1 macrophages. The underlying mechanism driving this polarization shift involves the activation of the AMPK signaling pathway. In vitro, M2-conditioned medium significantly promoted Schwann cell proliferation and migration. In a chronic sciatic nerve constriction (CCI) rat model, PVDF treatment improved pain sensitivity, as shown by increased mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). Additionally, PVDF treatment reduced the CD80/CD206 (M1/M2) ratio, promoting an anti-inflammatory environment, and increased the NF200/S100 ratio, indicating enhanced axonal regeneration. RNA sequencing revealed that Schwann cells co-cultured with M2-conditioned medium upregulated Cell Adhesion Molecule (CAM), Ca+ signaling pathway, and Mitogen Activated Protein Kinases (MAPK), critical signal pathway for Schwann cell regeneration and nerve repair. Our findings suggest that PVDF's piezoelectric properties offer a novel strategy for modulating macrophage polarization and enhancing Schwann cell activity, providing a potential therapeutic approach for NP.

2025-12-01 | GSE311957 | GEO

Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis [MPN patients]

2014-06-03 | GSE54644 | GEO

Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis [HEL cell lines]

2014-06-03 | GSE54645 | GEO

Predicting gene level sensitivity to JAK-STAT signaling perturbation using a mechanistic-to-machine learning framework II

Project description:To inhibit JAK2 upon IL-6 and IL-10-induced JAK-STAT signaling and quantify gene expression in bone marrow derived macrophages (BMDMs). Bulk RNAseq was done on cytokine-stimulated BMDM with and without Fedratinib treatment in order to profile the JAK2-inhibited cytokine-induced response.

2023-08-07 | GSE231344 | 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