Surgical trauma in mice modifies the content of circulating extracellular vesicles
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ABSTRACT:
PROVIDER: PRJNA785446 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17091100.fastq.gz | Fastqsanger.gz | |||
| SRR17091101.fastq.gz | Fastqsanger.gz | |||
| SRR17091102.fastq.gz | Fastqsanger.gz | |||
| SRR17091103.fastq.gz | Fastqsanger.gz | |||
| SRR17091104.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: Aseptic tissue injuries including major surgeries are associated with structural and functional changes in the brain suggesting the existence of periphery-to-brain communication. However, the nature of the carriers of such signaling remains largely unknown. Analyzis of the miRNAome and proteome of circulating extracellular vesicles (EVs) to evaluate their potential contribution to the periphery-to-brain signaling. Methods: EVs were isolated from the serum of the mice subjected to a tibia surgery after 6, 24, and 72 h, using Exoquick ULTRA commercial ki. Proteome and miRNAome were mapped using mass spectrometry and RNA-seq approaches. Results: Next-generation sequencing of small RNA libraries prepared from the total RNA isolated from the mouse serum EVs detected 252 miRNAs. Differential expression analysis using DESeq2 statistical package revealed 50 dysregulated miRNAs in the 24 h post-surgery EVs. The surgery effect declines after 72 h as judged by the lower number of dysregulated miRNAs. The differentially expressed miRNAs were examined by the DIANA-miRPath online tool that predicted dysregulation of several KEGG pathways including pathways involved in the lipid metabolism, ECM-receptor interaction, gap junction, various signal transduction pathways. Conclusions: The main question of the current project, is the surgery capable of modifying the expression of cargo molecules in circulating EVs, can be answered positively. Moreover, differential expression of a specific set of miRNAs in the “surgical” EVs suggests that they can be involved in the regulation of several metabolic pathways, such as ECM-receptor interaction and lipid metabolism in the recipient tissues, which is consistent with our data on hippocampal metabolic and functional dysregulation after surgery We conclude that surgery alters the EV composition in the blood, which paves the way for further studies on the functional effects of these EVs on the brain.
2022-01-08 | GSE189972 | GEO
Project description:Surgical interventions rapidly trigger a cascade of molecular, cellular and neural signaling responses that ultimately reach remote organs, including the brain. Using a mouse model of orthopedic surgery, we have previously demonstrated hippocampal metabolic, structural, and functional changes associated with cognitive impairment. However, the nature of the underlying signals responsible for such periphery-to-brain communication remains hitherto elusive. This is the first exploratory study that tests the hypothesis of extracellular vesicles (EVs) as potential mediators carrying information from the injured tissue to the distal organs including the brain. The primary goal was to investigate whether the cargo of circulating EVs after surgery can undergo quantitative changes that could potentially trigger phenotypic modifications in the target tissues. EVs were isolated from the serum of the mice subjected to a tibia surgery after 6, 24, and 72 h, and the proteome and miRNAome were investigated using mass spectrometry and RNA-seq approaches. We found substantial differential expression of proteins and miRNAs starting at 6 h post-surgery and peaking at 24 h. Interestingly, one of the up-regulated proteins at 24 h was α-synuclein, a pathogenic hallmark of certain neurodegenerative syndromes. We conclude that surgery alters the cargo of circulating EVs in the blood, and our results suggest EVs as potential systemic signal carriers mediating remote effects of surgery on the brain.
2022-01-08 | PXD030167 | Pride
Project description:Surgical interventions rapidly trigger a cascade of molecular, cellular, and neural signaling responses that ultimately reach remote organs, including the brain. Using a mouse model of orthopedic surgery, we have previously demonstrated hippocampal metabolic, structural, and functional changes associated with cognitive impairment. However, the nature of the underlying signals responsible for such periphery-to-brain communication remains hitherto elusive. Here we present the first exploratory study that tests the hypothesis of extracellular vesicles (EVs) as potential mediators carrying information from the injured tissue to the distal organs including the brain. The primary goal was to investigate whether the cargo of circulating EVs after surgery can undergo quantitative changes that could potentially trigger phenotypic modifications in the target tissues. EVs were isolated from the serum of the mice subjected to a tibia surgery after 6, 24, and 72 h, and the proteome and miRNAome were investigated using mass spectrometry and RNA-seq approaches. We found substantial differential expression of proteins and miRNAs starting at 6 h post-surgery and peaking at 24 h. Interestingly, one of the up-regulated proteins at 24 h was α-synuclein, a pathogenic hallmark of certain neurodegenerative syndromes. Analysis of miRNA target mRNA and corresponding biological pathways indicate the potential of post-surgery EVs to modify the extracellular matrix of the recipient cells and regulate metabolic processes including fatty acid metabolism. We conclude that surgery alters the cargo of circulating EVs in the blood, and our results suggest EVs as potential systemic signal carriers mediating remote effects of surgery on the brain.
| S-EPMC8804340 | biostudies-literature
Project description:Purpose The aim of this study was to determine the fracture hematoma (fxH) proteome after multiple trauma using label free proteomics, comparing two different established surgical treatment strategies. Basic procedures A large animal (sus scrofa), multiple trauma animal model was used in which two different trauma surgical treatment methods were compared: Early Total Care (ETC) versus Damage Control Orthopedics (DCO). fxH was harvested after 72 hours and analyzed using liquid chromatography-tandem mass spectrometry. Protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase. Main findings The proteome of the early fxH was characterized by immunomodulatory and osteogenic proteins, as well as proteins involved in the coagulation cascade. Distinct, treatment-specific proteome alterations were observed. The fxH proteome of the ETC group showed increased expression of pro-inflammatory proteins related to, among others, activation of the complement system, neutrophil functioning, and macrophage activation, while showing decreased expression of proteins related to osteogenesis and tissue remodeling. On the other hand, the fxH proteome of the DCO group contained various upregulated or exclusively detected proteins related to tissue regeneration and remodeling, as well as proteins related to anti-inflammatory and osteogenic processes. Principal conclusions The early fxH proteome of the ETC group was characterized by the expression of immunomodulatory, mainly pro-inflammatory, proteins, whereas the early fxH proteome of the DCO group was more regenerative and osteogenic in nature. These findings match clinical observations, in which enhanced surgical trauma after severe multiple trauma causes dysbalanced inflammation, potentially leading to reduced tissue regenerative capabilities, and gained insights into regulatory mechanisms of fracture healing after severe trauma.
2024-05-24 | PXD049002 | Pride
Project description:Abstract Background: Several studies on the use of erythropoietin (Epo) to treat anaemia in patients undergoing cancer treatment have shown adverse effects on tumour control and survival. Experimental studies indicate that this could be linked to an interaction with wound healing processes and not an effect on tumour cells per se. We have previously shown that erythropoietin in combination with surgical trauma stimulates tumour growth. In the present study, we investigated the effect of surgery and Epo on gene expression. Methods: Human tumours from oral squamous cell cancer were xenotransplanted to nude mice treated with Epo. The tumours were then transected in a standardised procedure to mimic surgical trauma and the change in gene expression of the tumours was investigated by microarray analysis. qRT-PCR was used to measure the levels of mRNAs of pro-apoptotic genes. The frequency of apoptosis in the tumours was assessed using immunohistochemistry for caspase-3. Results: There was little change in the expression of genes involved in tumour growth and angiogenesis but a significant down-regulation of the expression of genes involved in apoptosis. This effect on apoptosis was confirmed by a general decrease in the expression of mRNA for selected pro-apoptotic genes. Epo-treated tumours had a significantly lower frequency of apoptosis as measured by immunohistochemistry for caspase 3. Conclusions: Our results suggest that the increased tumour growth during erythropoietin treatment might be due to inhibition of apoptosis, an effect that becomes significant during tissue damage such as surgery. This further suggests that the decreased tumour survival during erythropoietin treatment might be due to inhibition of apoptosis. Key words: Erythropoietin, Head and neck cancer, surgery, apoptosis, wound healing, xenograft. We wanted to study the effect of wound healing mechanisms on remaining tumour tissue efter incomplete surgery or biopsy. We xenografted human Head and Neck squamous Cell Cancer (HNSCC) tumours on Balb/c nude mice. The mice were divided in six groups. Three of the groups received intrapertoneal doses of erythropoietin (Epo) and the other three groups were given NaCl as placebo. One treated and one non-treated group were harvested without surgical transection. In the other four groups, the tumours were transected mimicking subtotal surgery. One Epo-treated and one non-treated group was analysed after 24 hours after transection and the remaining two groups 48 hours after surgery. Groups C and D were not analyzed due to harvesting at an unsuitable time interval. Group A No surgery (=FALSE) + Epo Group B No surgery (=FALSE) + NaCl Group E Surgery (=TRUE) + Epo 24 hours after surgical transection Group F Surgery (=TRUE) + NaCl 24 hours after surgical resection Group G Surgery (=TRUE) + Epo 48 hours after surgical transection Group H Surgery (=TRUE) + Nacl 48 hours after surgical transection
2014-06-04 | E-GEOD-58194 | biostudies-arrayexpress
Project description:Abstract Background: Several studies on the use of erythropoietin (Epo) to treat anaemia in patients undergoing cancer treatment have shown adverse effects on tumour control and survival. Experimental studies indicate that this could be linked to an interaction with wound healing processes and not an effect on tumour cells per se. We have previously shown that erythropoietin in combination with surgical trauma stimulates tumour growth. In the present study, we investigated the effect of surgery and Epo on gene expression. Methods: Human tumours from oral squamous cell cancer were xenotransplanted to nude mice treated with Epo. The tumours were then transected in a standardised procedure to mimic surgical trauma and the change in gene expression of the tumours was investigated by microarray analysis. qRT-PCR was used to measure the levels of mRNAs of pro-apoptotic genes. The frequency of apoptosis in the tumours was assessed using immunohistochemistry for caspase-3. Results: There was little change in the expression of genes involved in tumour growth and angiogenesis but a significant down-regulation of the expression of genes involved in apoptosis. This effect on apoptosis was confirmed by a general decrease in the expression of mRNA for selected pro-apoptotic genes. Epo-treated tumours had a significantly lower frequency of apoptosis as measured by immunohistochemistry for caspase 3. Conclusions: Our results suggest that the increased tumour growth during erythropoietin treatment might be due to inhibition of apoptosis, an effect that becomes significant during tissue damage such as surgery. This further suggests that the decreased tumour survival during erythropoietin treatment might be due to inhibition of apoptosis. Key words: Erythropoietin, Head and neck cancer, surgery, apoptosis, wound healing, xenograft.
2014-06-04 | GSE58194 | GEO
Project description:comparison miRNA content between extracellular vesicles from AAV-transduced or intact cells
2021-08-07 | E-MTAB-10858 | biostudies-arrayexpress
Project description:#G017 Burn/Trauma Study. This is a Glue Grant Study comparison between gene expression analyses performed in eight trauma/burn subjects using either a buffy coat isolation of whole blood or using the PAXgene system Keywords: other
2004-04-24 | GSE1343 | GEO
Project description:IntroductionTwo trauma treatment principles are Early Total Care (ETC), and Damage Control Orthopedics (DCO). Cellular mechanisms that underlie the connection between treatment type, its systemic effects, and tissue regeneration are not fully known. Therefore, this study aimed to: 1) profile microRNA (miRNA) expression in plasma derived Extracellular Vesicles (EVs) from a porcine multiple trauma model at different timepoints, comparing two surgical treatments; and 2) determine and validate the miRNA's messengerRNA (mRNA) targets.MethodsThe porcine multiple trauma model consisted of blunt chest trauma, liver laceration, bilateral femur fractures, and controlled haemorrhagic shock. Two treatment groups were defined, ETC (n=8), and DCO (n=8). Animals were monitored under Intensive Care Unit-standards, blood was sampled at 1.5, 2.5, 24, and 72 hours after trauma, and EVs were harvested from plasma. MiRNAs were analysed using quantitative Polymerase Chain Reaction arrays. MRNA targets were identified in silico and validated in vivo in lung and liver tissue.ResultsThe arrays showed distinct treatment specific miRNA expression patterns throughout all timepoints, and miRNAs related to the multiple trauma and its individual injuries. EV-packed miRNA expression in the ETC group was more pro-inflammatory, indicating potentially decreased tissue regenerative capacities in the acute post-traumatic phase. In silico target prediction revealed several overlapping mRNA targets among the identified miRNAs, related to inflammation, (pulmonary) fibrosis, and Wnt-signalling. These were, among others, A Disintegrin and Metalloproteinase domain-containing protein 10, Collagen Type 1 Alpha 1 Chain, Catenin Beta Interacting Protein 1, and Signal Transducers and Activators of Transcription 3. Validation of these mRNA targets in the lung showed significant, treatment specific deregulations which matched the expression of their upstream miRNAs. No significant mRNA deregulations were observed in the liver.DiscussionThis study showed treatment specific, EV-packed miRNA expression patterns after trauma that correlated with mRNA expressions in the lungs, target organs over distance. A systemic response to the increased surgical trauma in the ETC group was identified, with various miRNAs associated with injuries from the trauma model, and involved in (systemic) inflammation, tissue regeneration. EV-transported miRNAs demonstrated a clear role in multiple trauma, warranting further research into tissue-tissue talk and therapeutic applications of EVs after trauma.
| S-EPMC10626999 | biostudies-literature
Project description:Small extracellular vesicles propagate the inflammatory response after trauma.
| PRJNA722432 | ENA