A comprehensive immune cell atlas of cystic kidney disease reveals the involvement of adaptive immune cells in injury mediated cyst progression
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE193528 | GEO | 2022/01/19
REPOSITORIES: GEO
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Project description:A comprehensive immune cell atlas of cystic kidney disease reveals the involvement of adaptive immune cells in injury mediated cyst progression
| PRJNA796540 | ENA
Project description:Biomarkers for early detection of chronic kidney disease are needed, as millions of patients suffer from chronic diseases predisposing them to kidney failure. Protein microarrays may hold utility in the discovery of auto-antibodies in other conditions not commonly considered auto-immune diseases. We hypothesized that proteins are released as a consequence of damage at a cellular level during end-organ damage from renal injury, not otherwise recognized as self-antigens, and an adaptive humoral immune response to these proteins might be detected in the blood, as a non-invasive tracker of this injury. The resultant antibodies (Ab) detected in the blood would serve as effective biomarkers for occult renal injury, enabling earlier clinical detection of chronic kidney disease than currently possible, due to the redundancy of the serum creatinine as a biomarker for early kidney injury. To screen for novel autoantibodies in chronic kidney disease, 24 protein microarrays were used to compare serum Ab from patients with chronic kidney disease against matched controls. From a panel of 38 antigens with increased Ab binding, 4 were validated in 71 individuals, with (n=50) and without (n=21) renal insufficiency. Significant elevations in the titer of novel auto-Ab were noted against Angiotensinogen (AGT) and PRKRIP1 in renal insufficiency. Current validation is underway to evaluate if these auto-Ab can provide means to follow the evolution of chronic kidney disease in patients with early stages of renal insufficiency, and if these rising titers of these auto-Ab correlate with the rate of progression of chronic kidney disease. Serum antibodies were profiled for 7 healthy individuals and 17 patients with chronic kidney disease, using the Invitrogen ProtoArray® Human Protein Microarray v3.0 platform (Invitrogen, Carlsbad, CA). This platform contains 5,056 non-redundant human proteins expressed in a baculovirus system, purified from insect cells and printed in duplicate onto a nitrocellulose-coated glass slide. Each protein is spotted twice on each array, to measure the quality of the signal intensity. Details for experiment processing and analysis follow the previous publication from our group (Li et al Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4148-53). Prospector software was used to retrieve the expression based on immune response profiling of the .gal files.
2010-08-12 | E-GEOD-23609 | biostudies-arrayexpress
Project description:Mice lacking the developmental axon guidance molecule EphA4 have previously been shown to exhibit extensive axonal regeneration and functional recovery following spinal cord injury. To assess mechanisms by which EphA4 may modify the response to neural injury, a microarray was performed on spinal cord tissue from mice with spinal cord injury and sham injured controls. RNA was purified from spinal cords of adult EphA4 knockout and wild-type mice four days following lumbar spinal cord hemisection or laminectomy only and was hybridised to Affymetrix All-Exon Array 1.0 GeneChips. While subsequent analyses indicated that several pathways were altered in EphA4 knockout mice, of particular interest was the attenuated or otherwise altered expression of a number of inflammatory genes, including Arginase 1, expression of which was lower in injured EphA4 knockout compared to wild-type mice. Immunohistological analyses of different cellular components of the immune response were then performed in injured EphA4 knockout and wild-type spinal cords. While numbers of infiltrating CD3+ T cells were low in the hemisection model, a robust CD11b+ macrophage / microglial response was observed post-injury. There was no difference in the overall number or spread of macrophages / activated microglia in injured EphA4 knockout compared to wild-type spinal cords at two, four or fourteen days post-injury, however a lower proportion of Arginase-1 immunoreactive macrophages / activated microglia was observed in EphA4 knockout spinal cords at four days post-injury. Subtle alterations in the neuroinflammatory response in injured EphA4 knockout spinal cords may contribute to the regeneration and recovery observed in these mice following injury. Comparison was made between gene expression in wild-type and knockout samples both before and after injury. 3 replicates per group.
2012-05-23 | E-GEOD-34430 | biostudies-arrayexpress
Project description:The aneurysm clip impact-compression model of spinal cord injury (SCI) in animals mimics the primary mechanism of SCI in human, i.e. acute impact and persisting compression; and its histo-pathological and behavioural outcomes are extensively similar to the human SCI. In order to understand the distinct molecular events underlying this injury model, an analysis of global gene expression of the acute, subacute and chronic stages of a moderate to severe injury to the rat spinal cord was conducted using a microarray gene chip approach. Rat thoracic spinal cord (T7) was injured using aneurysm clip impact-compression injury model and the epicenter area of injured spinal cord was isolated for RNA extraction and processing and hybridization on Affymetrix GeneChip arrays.
2013-11-15 | E-GEOD-45006 | biostudies-arrayexpress
Project description:Transcriptional profiling of Biomphalaria snail (whole body tissues) comparing BS90 strain untreated with sterile wounding and septic injury using a new comprehensive microarray platform design. Goal was to compare responses to differen immune challenges within one strain. Three-condition experiment one strain untreated vs. injury vs. septic injury, Biological replicates: 2 control replicates, 3 injured replicates, 2 septic injury replicates.
2016-07-30 | E-GEOD-71054 | biostudies-arrayexpress
Project description:To shed light on the early processes of immune response to peripheral nerve injury, we first used genome-wide transcriptional profiling and bioinformatics (Ingenuity, NextBio) pathway analyses of the proximal (P; regenerating) and distal (D; degenerating) nerve stumps at day 1 in the sciatic nerve axotomy model in rats. We identified a number of specific immunomodulatory genes and pathways that were regulated shortly post-injury in both the P and D segments, including all members of the interleukin (IL), chemokine, tumor necrosis factor (TNF), matrix metalloproteinase (MMP), toll-like receptor (TLR), tissue inhibitor of metalloproteinase (TIMP), ion channel and myosin families. Immunomodulatory calcium-binding S100A8 and S100A9 were the top up-regulated genes in both the D and P segments. In cultured Schwann cells stimulated with the purified S100A8/A9 heterodimer we recorded a high level of similarity of the activated genes and pathways with that of the injured nerve, especially in the activation of the chemokine and cytokine gene networks that support agranulocyte and granulocyte chemotaxis, adhesion, transmigration and rolling signaling pathways. We also confirmed activation of multiple cell death related gene networks supporting TNFR1, natural killer cell receptor and death receptor apoptosis signaling in the D stump, and the gluconeogenesis/glycolysis and cytoskeletal motility signaling in the P stump, corroborated by activation of ERK, PI3K and JNK kinase pathways. As compared to the D segment, multiple additional pathways were more efficiently upregulated in the P stump, including the IL-6 and -17, MMP-9, calcium, activated agranulocyte, leukocyte rolling and glutathione-mediated detoxification signaling pathways. These data suggest that shortly after nerve injury, upregulation of S100A8/A9 is responsible for the expression and release of chemokines and cytokines by Schwann cells, necessary to generate the initial chemotactic gradient and guide the hematogenous immune cells into the injury site. Gene expression profiling of total RNAs extracted from injured and non-injured rat sciatic nerves, and primary rat Schwann cells stimulated with S100A8/A9 proteins
2015-01-01 | E-GEOD-62282 | biostudies-arrayexpress
Project description:We describe ubiquitomics and proteomics analysis of porcine articular cartilage post mechanical injury. Analysis showed ubiquitin peptides differentially enriched post injury compared to non injured controls.
2022-12-19 | PXD030817 | Pride
Project description:Although injury in glomerular disease might only damage a subset of podocytes in any given glomerulus, the response of the healthy neighboring podocytes to the injured podocytes oftentimes determines the course of the disease. To investigate this relationship, we designed a dual chamber open microfluidic co-culture device to specifically examine paracrine signaling to healthy podocytes from podocytes targeted injured by either Adriamycin, Puromycin Aminonucleoside or a cytopathic anti-podocyte antibody. Global transcriptomic analysis measured by RNA-sequencing revealed shared and unique pathways between the three forms of targeted injury, with temporal differences in the transcriptomic responses to each form of injury. Paracrine-induced injury to neighboring podocytes was similar to the targeted primary injured podocytes and was specific for each podocyte injury model. Ligand-receptor analysis of ligands secreted by the insult targeted podocytes and receptors expressed by the responsive, paracrine injured counterparts identified 23 candidate mediator pairs. These findings critically define a new concept for future studies to understand the pathways involved in secondary cellular injury fields in animal models and ultimately human studies.
2025-09-01 | GSE255482 | GEO
Project description:Primary afferent collateral sprouting (PACS) is a process whereby non-injured primary afferent neurons respond to some stimulus by extending new branches from existing axons. In the model used here (spared dermatome), the intact sensory neurons respond to the denervation of adjacent areas of skin by sprouting new axon branches into that adjacent denervated territory. Neurons of both the central and peripheral nervous systems undergo this process, which contributes to both adaptive and maladaptive plasticity. Investigations of gene expression changes associated with PACS can provide a better understanding of the molecular mechanisms controlling this process. Consequently, it can be used to develop treatment for spinal cord injury to promote functional recovery. In this study, we sought to identify gene expression changes in PACS using 20 Affymetrix Rat Genome 230 2.0 microarrays. The experiments were designed to discover global gene expression changes in non-injured DRG neurons undergoing PACS. T11 DRG neurons remained intact and undergo PACS after the cutaneous nerves of the adjacent segments (T9, T10, T12, and T13) were injured and regeneration of those injured nerves prevented by ligation. Thus, the T9, T10, T12, and T13 dermatomes were denervated, but the T11 dermatome remained intact. Axons of the T11dermatome (and thus housed in the T11 dorsal root ganglion (DRG)), extended new branches to innervate the T9, T10, T12, and T13 dermatomes. N.B.: This is NOT a spared root experiment. ALL spinal roots were non-injured. Peripheral nerves were used. A total of 20 Affymetrix Rat Genome 230 2.0 microarrays were analyzed: six naïve controls, seven replicates at day 7 post-surgery (presumed to represent an â??initiation phaseâ??), and seven replicates at day 14 post-surgery (presumed to represent a â??maintenance phaseâ??). DRGs were NOT pooled onto microarrays. Each animal had its own microarray with T11 DRG sample which underwent 2-round amplification. After quality control analysis, one of the naïve control microarrays was removed from further analysis.
2016-03-01 | E-GEOD-72551 | biostudies-arrayexpress
Project description:Acute inflammatory exacerbations (AIEs) represent immune-driven deteriorations of many chronic lung conditions, including COPD, asthma, and pulmonary fibrosis (PF). The first line of therapy is represented by broad-spectrum immunomodulation. To better study immune cell heterogeneity during AIE-PF, this work leverages a clinically relevant model of inflammatory exacerbations triggered by mutation in the alveolar epithelial type 2 cell Surfactant Protein-C gene [SP-CI73T]. SP-CI73T mice received corn oil (controls) or tamoxifen (175 mg/kg, orally) to excise a neomycin cassette placed on the surfacant protein C gene locus, hence inducing the expression of the mutant transcript. We have previously shown that a complex inflammatory response arises by 14 days post tamoxifen administration. Paraffin sections of murine lungs were therefore collected in controls and 14 days post induction. Immunofluorescence for DNA, CD45, CD68 was performed to identify macrophages (CD45+CD68+) and non-immune ("other", DNA+CD45-) cells within healthy, peri-injured and injured regions of the lung. A total of 12 regions (680um x 700um in size) were selected and macrophages and "other" cells isolated. RNA sequencing was then performed. Principal component and pathway analysis revealed spatial heterogeneity with an hyperactive peri-injured compartment (extracellular matrix remodeling, innate and adaptive immunity, senescence). Cells isolated from injured areas of the lung were relatively quiescent. These results illustrate regional heterogeneity in immune and non-immune cells of the lung during fibrogenic stress.
2024-07-24 | GSE264128 | GEO