56 research outputs found
Healthy-IgAN urine proteomics RAW MS files
No full textRAW files from Q-Exactive MS/MS analysisHealthy Urine1Healthy Urine2IgAN Urine1IgAN Urine
Table_5_Comparative Transcriptomics of Rat and Axolotl After Spinal Cord Injury Dissects Differences and Similarities in Inflammatory and Matrix Remodeling Gene Expression Patterns.XLSX
No full textFollowing spinal cord injury in mammals, maladaptive inflammation, and matrix deposition drive tissue scarring and permanent loss of function. In contrast, axolotls regenerate their spinal cord after severe injury fully and without scarring. To explore previously unappreciated molecules and pathways that drive tissue responses after spinal cord injury, we performed a 4-way intersection of rat and axolotl transcriptomics datasets and isolated shared genes with similar or differential expression at days 1, 3, and 7 after spinal cord injury in both species. Systems-wide differences and similarities between the two species are described in detail using public-domain computational tools and key differentially regulated genes are highlighted. Amongst persistent differential expression in matching neuronal genes (upregulated in axolotls but downregulated in rats) and nucleic acid metabolism genes (downregulated in axolotls but upregulated in rats), we found multiple extracellular matrix genes that were upregulated in both species after spinal cord injury and all time-points (days 1, 3, and 7), indicating the importance of extracellular matrix remodeling in wound healing. Moreover, the archetypal transcription factor SP1, which was consistently upregulated in rats but was unchanged in axolotls, was predicted as a potential transcriptional regulator of classic inflammatory response genes in rats most of which were not regulated in regenerating axolotls. This analysis offers an extensive comparative platform between a non-regenerating mammal and a regenerating urodele after spinal cord injury. To better understand regeneration vs. scarring mechanisms it is important to understand consistent molecular differences as well as similarities after experimental spinal cord injury.</p
The Expression of Inflammatory Mediators in Bladder Pain Syndrome
No full textDesign, setting, and participants: Fifteen women with BPS and 15 women with stress urinary incontinence without bladder pain were recruited from Cork University Maternity Hospital from October 2011 to October 2012. During cystoscopy, 5-mm bladder biopsies were taken and processed for gene expression analysis. The effect of the identified genes was tested in laboratory animals. Outcome measures and statistical analysis: We studied the expression of 96 inflammation related genes in diseased and healthy bladders. We measured the correlation between genes and patient clinical profiles using the Pearson correlation coefficient. Results and limitations: Analysis revealed 15 differentially expressed genes, confirmed in a replication study. FGF7 and CCL21 correlated significantly with clinical outcomes. Intravesical CCL21 instillation in rats caused increased bladder excitability and increased c-fos activity in spinal cord neurons. CCL21 atypical receptor knockout mice showed significantly more c-fos upon bladder stimulation with CCL21 than wild-type littermates. There was no change in FGF7-treated animals. The variability in patient samples presented as the main limitation. We used principal component analysis to identify similarities within the patient group. Conclusions: Our study identified two biologically relevant inflammatory mediators in BPS and demonstrated an increase in nociceptive signalling with CCL21. Manipulation of this ligand is a potential new therapeutic strategy for BPS. Patient summary: We compared gene expression in bladder biopsies of patients with bladder pain syndrome (BPS) and controls without pain and identified two genes that were increased in BPS patients and correlated with clinical profiles. We tested the effect of these genes in laboratory animals, confirming their role in bladder pain. Manipulating these genes in BPS is a potential treatment strategy
Analysed Microarray (GSE45006) Rat T8 SCI 7 days post-SCI - Supplementary Table 1
No full textAnalysed Microarray Rat T8 SCI 7 days post-SCI - Table 1
- 4 sham (control) T8 spinal cord segments
- 4 injured T8 spinal cord segments
7 days post-SCI
T8 aneurysm clip compression SCI
Primary data freely accessible online via the gene expression omnibus (GSE45006):
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45006
Transcriptomics microarray published by:
Chamankhah M et al, (2013) Genome-wide gene expression profiling of stress response in a spinal cord clip compression injury model BMC Genomics 14, 583.
https://www.ncbi.nlm.nih.gov/pubmed/2398490
The Expression of Inflammatory Mediators in Bladder Pain Syndrome
No full textDesign, setting, and participants: Fifteen women with BPS and 15 women with stress urinary incontinence without bladder pain were recruited from Cork University Maternity Hospital from October 2011 to October 2012. During cystoscopy, 5-mm bladder biopsies were taken and processed for gene expression analysis. The effect of the identified genes was tested in laboratory animals. Outcome measures and statistical analysis: We studied the expression of 96 inflammation related genes in diseased and healthy bladders. We measured the correlation between genes and patient clinical profiles using the Pearson correlation coefficient. Results and limitations: Analysis revealed 15 differentially expressed genes, confirmed in a replication study. FGF7 and CCL21 correlated significantly with clinical outcomes. Intravesical CCL21 instillation in rats caused increased bladder excitability and increased c-fos activity in spinal cord neurons. CCL21 atypical receptor knockout mice showed significantly more c-fos upon bladder stimulation with CCL21 than wild-type littermates. There was no change in FGF7-treated animals. The variability in patient samples presented as the main limitation. We used principal component analysis to identify similarities within the patient group. Conclusions: Our study identified two biologically relevant inflammatory mediators in BPS and demonstrated an increase in nociceptive signalling with CCL21. Manipulation of this ligand is a potential new therapeutic strategy for BPS. Patient summary: We compared gene expression in bladder biopsies of patients with bladder pain syndrome (BPS) and controls without pain and identified two genes that were increased in BPS patients and correlated with clinical profiles. We tested the effect of these genes in laboratory animals, confirming their role in bladder pain. Manipulating these genes in BPS is a potential treatment strategy
Persistent Alterations in Microglial Enhancers in a Model of Chronic Pain
No full textSummary Chronic pain is a common and devastating condition that induces well-characterized changes in neurons and microglia. One major unanswered question is why these changes should persist long after the precipitating injury has healed. Here, we suggest that some of the longer-lasting consequences of nerve injury may be hidden in the epigenome. Cell sorting and sequencing techniques were used to characterize the spinal cord immune response in a mouse model of chronic neuropathic pain. Infiltration of peripheral myeloid cells was found to be absent, and RNA sequencing (RNA-seq) of central microglia revealed transient gene expression changes in response to nerve ligation. Conversely, examination of microglial enhancers revealed persistent, post-injury alterations in close proximity to transcriptionally regulated genes. Enhancers are regions of open chromatin that define a cell’s transcription factor binding profile. We hypothesize that changes at enhancers may constitute a mechanism by which painful experiences are recorded at a molecular level
Proteomics Analysis of Cardiac Extracellular Matrix Remodeling in a Porcine Model of Ischemia/Reperfusion Injury
No full textBackground-After myocardial ischemia, extracellular matrix (ECM) deposition occurs at the site of the focal injury and at the border region. Methods and Results-We have applied a novel proteomic method for the analysis of ECM in cardiovascular tissues to a porcine model of ischemia/reperfusion injury. ECM proteins were sequentially extracted and identified by liquid chromatography tandem mass spectrometry. For the first time, ECM proteins such as cartilage intermediate layer protein 1, matrilin-4, extracellular adipocyte enhancer binding protein 1, collagen alpha-1(XIV), and several members of the small leucine-rich proteoglycan family, including asporin and prolargin, were shown to contribute to cardiac remodeling. A comparison in 2 distinct cardiac regions (the focal injury in the left ventricle and the border region close to the occluded coronary artery) revealed a discordant regulation of protein and mRNA levels; although gene expression for selected ECM proteins was similar in both regions, the corresponding protein levels were much higher in the focal lesion. Further analysis based on > 100 ECM proteins delineated a signature of early-and late-stage cardiac remodeling with transforming growth factor-beta 1 signaling at the center of the interaction network. Finally, novel cardiac ECM proteins identified by proteomics were validated in human left ventricular tissue acquired from ischemic cardiomyopathy patients at cardiac transplantation. Conclusion-Our findings reveal a biosignature of early-and late-stage ECM remodeling after myocardial ischemia/reperfusion injury, which may have clinical utility as a prognostic marker and modifiable target for drug discovery. (Circulation. 2012; 125: 789-802.
Extracellular matrix composition and remodeling in human abdominal aortic aneurysms: a proteomics approach.
No full textAbdominal aortic aneurysms (AAA) are characterized by pathological remodeling of the aortic extracellular matrix (ECM). However, besides the well-characterized elastolysis and collagenolysis little is known about changes in other ECM proteins. Previous proteomics studies on AAA focused on cellular changes without emphasis on the ECM. In the present study, ECM proteins and their degradation products were selectively extracted from aneurysmal and control aortas using a solubility-based subfractionation methodology and analyzed by gel-liquid chromatography-tandem MS and label-free quantitation. The proteomics analysis revealed novel changes in the ECM of AAA, including increased expression as well as degradation of collagen XII, thrombospondin 2, aortic carboxypeptidase-like protein, periostin, fibronectin and tenascin. Proteomics also confirmed the accumulation of macrophage metalloelastase (MMP-12). Incubation of control aortic tissue with recombinant MMP-12 resulted in the extensive fragmentation of these glycoproteins, most of which are novel substrates of MMP-12. In conclusion, our proteomics methodology allowed the first detailed analysis of the ECM in AAA and identified markers of pathological ECM remodeling related to MMP-12 activity
Table_1_Comparative Transcriptomics of Rat and Axolotl After Spinal Cord Injury Dissects Differences and Similarities in Inflammatory and Matrix Remodeling Gene Expression Patterns.XLSX
No full textFollowing spinal cord injury in mammals, maladaptive inflammation, and matrix deposition drive tissue scarring and permanent loss of function. In contrast, axolotls regenerate their spinal cord after severe injury fully and without scarring. To explore previously unappreciated molecules and pathways that drive tissue responses after spinal cord injury, we performed a 4-way intersection of rat and axolotl transcriptomics datasets and isolated shared genes with similar or differential expression at days 1, 3, and 7 after spinal cord injury in both species. Systems-wide differences and similarities between the two species are described in detail using public-domain computational tools and key differentially regulated genes are highlighted. Amongst persistent differential expression in matching neuronal genes (upregulated in axolotls but downregulated in rats) and nucleic acid metabolism genes (downregulated in axolotls but upregulated in rats), we found multiple extracellular matrix genes that were upregulated in both species after spinal cord injury and all time-points (days 1, 3, and 7), indicating the importance of extracellular matrix remodeling in wound healing. Moreover, the archetypal transcription factor SP1, which was consistently upregulated in rats but was unchanged in axolotls, was predicted as a potential transcriptional regulator of classic inflammatory response genes in rats most of which were not regulated in regenerating axolotls. This analysis offers an extensive comparative platform between a non-regenerating mammal and a regenerating urodele after spinal cord injury. To better understand regeneration vs. scarring mechanisms it is important to understand consistent molecular differences as well as similarities after experimental spinal cord injury.</p
The -omics era: Proteomics and lipidomics in vascular research
No full textA main limitation of the current approaches to atherosclerosis research is the focus on the investigation of individual factors, which are presumed to be involved in the pathophysiology and whose biological functions are, at least in part, understood. These molecules are investigated extensively while others are not studied at all. In comparison to our detailed knowledge about the role of inflammation in atherosclerosis, little is known about extracellular matrix remodelling and the retention of individual lipid species rather than lipid classes in early and advanced atherosclerotic lesions. The recent development of mass spectrometry-based methods and advanced analytical tools are transforming our ability to profile extracellular proteins and lipid species in animal models and clinical specimen with the goal of illuminating pathological processes and discovering new biomarkers. (C) 2011 Elsevier Ireland Ltd. All rights reserved
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