Identification of enhancer elements that direct long-range responses to tissue injury
Ontology highlight
ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE158079 | GEO | 2022/02/25
REPOSITORIES: GEO
Similar Datasets
Project description:In previous studies, we identified and demonstrated that a 1.2kb cebpd downstream element (CEN) is capable and neccessary for the induction of cebpd in the kidney after cardiac injury. The goal of this study is to unveal the Cebpd regulated responses of kidney to cardiac regeneration in zebrafish. we profiled responses by kidney in cebpd mutant and enhancer (CEN) mutant fish zebrafish to massive injuries of the heart.
2022-02-25 | GSE193630 | GEO
Project description:Common acute injuries to skeletal muscle can lead to significant pain and disability. The current therapeutic approaches for treating muscle injuries are dependent on the clinical severity but not on the type of injury. The aim of this study was to compare the molecular events accompanying the degeneration and repair phases of contraction- and trauma-induced muscle injuries by applying DNA microarray methodology to two well-characterized mouse models of skeletal muscle injury, i.e., eccentric contraction-induced injury (CI) and traumatic injury induced by freezing (FI). Histopathological evaluation and measurements of muscle strength were accompanied by analyses of expression for 12,488 known genes at four time points ranging from 6 hours to 7 days post-injury. Real-time RT-PCR was used to confirm some of the gene expression temporal profiles. While both types of injury cause early induction of transcription, myogenic, and stress-responsive factors, they also induce injury type-specific gene expression profiles. CI only activates a set of genes associated with the protection and repair of protein and structural integrity while FI activates gene sets which result in extensive inflammatory responses, tissue remodeling, angiogenesis, and myofibre and extracellular matrix synthesis. This study identified genes that are candidates for therapeutic manipulation following two disparate types of muscle injury. Experiment Overall Design: 2 types of skeletal muscle injury (eccentric contraction- and freeze-induced) x 4 time points after injury (6 hours, 1 day, 3 days, and 7 days post-injury). There were 3 samples for each of the 8 cells with the exception of the 'contraction injury, 1 day post-injury' and 'freeze injury, 7 days post-injury' cells; for each of these 2 cells, there were only 2 samples. Additionally, there were 3 control (i.e., uninjured) muscle samples.
2007-11-22 | E-GEOD-5413 | biostudies-arrayexpress
Project description:Traumatic brain injury (TBI) pathologies are caused by primary and secondary injuries. Primary injuries result from physical damage to the brain, and secondary injuries arise from cellular responses to primary injuries. A characteristic cellular response is sustained activation of inflammatory pathways commonly mediated by NF-B transcription factors. Using a Drosophila melanogaster TBI model, we previously found that the main proximal transcriptional response to primary injuries is triggered by activation of Toll and Imd innate immune response pathways that engage NF-B factors Dif and Relish (Rel), respectively. Here, we monitor the abundance of Rel protein by mass spectrometry (MS) and observe that Rel increases in fly heads at 4-8 h after TBI. To investigate the necessity of Rel for secondary injuries, we generated a null allele, Reldel, by CRISPR/Cas9 editing. Heterozygous but not homozygous Reldel mutation reduced mortality at 24 h after TBI and increased the lifespan of injured flies. Additionally, the effect of heterozygous Reldel mutation on mortality was modulated by genetic background and diet. To identify genes that facilitate effects of heterozygous Reldel mutation on TBI outcomes, we compared genome-wide mRNA expression profiles of uninjured and injured +/+, +/Reldel, and Reldel/Reldel flies at 4 h following TBI. Only a few genes changed expression more than two-fold in +/Reldel flies relative to +/+ and Reldel/Reldel flies, and they were not canonical innate immune response genes. Therefore, Rel is necessary for TBI-induced secondary injuries but in complex ways involving Rel gene dose, genetic background, diet, and possibly small changes in expression of innate immune response genes.
2020-12-04 | PXD021869 | Pride
Project description:This laboratory works on selectins and their carbohydrate ligands in lymphocyte homing and inflammation. The lab also studies heparin-degrading endosulfatases and their roles in regulating the interactions of growth factors and morphogens with proteoglycans. The purpose of the experiment is to examine gene expression profiles in spinal cords of injured as a function of time after a contusion injury. The tissue will be generated in the lab of Linda Noble, Professor in the Department of Neurological Surgery at UCSF who is an expert on the pathogenesis of spinal cord injury. Wild-type male C57B/6 mice (8-10 weeks of age) were used. Injuries were produced by contusion. Spinal cords from control mice (uninjured) and experimental (injured) mice were processed (4 and 7 days after injury). A 3 mm length of spinal cord (centered at the injury) and a 3 mm segment from a distant site were isolated from each animal. Tissue from 3 mice were pooled for each sample. Three replicate samples per treatment group were processed for RNA. Thus, a total of 18 RNA samples were hybridized to 18 gene chips. The analysis will determine whether specific glycosylation changes accompany spinal cord injury. Of particular interest are changes in the sulfation profile of proteoglycan GAG chains (e.g., chondroitin sulfate) and in the appearance of potential carbohydrate ligands for infiltrating leukocytes bearing L-selectin or other endogenous lectins.
2011-02-17 | E-GEOD-27359 | biostudies-arrayexpress
Project description:We inflicted TBI to chemokine-deficient mouse lines in order to establish involvement of various signalling pathways that may be addressed therapeutically. Interacting chemokine pathways in brain regulate distinct inflammatory cells. Activated microglia are separate from invading phagocytes and dendritic cells. Findings show potential targets to interfere with specific inflammatory responses after brain injury. TBI was carried out in Ccl3-/- and Ccr2-/- mice, total RNA prepared from injured cerebral neocortex after three days. RNA samples were from uninjured Ccl3-/- and Ccr2-/- mice as reference for hybridization on Affymetrix microarrays.
2014-06-14 | E-GEOD-58483 | biostudies-arrayexpress
Project description:The response to acute myotoxic injury requires stimulation of local repair mechanisms in the damaged tissue. However, satellite cells in muscle distant from acute injury have been reported to enter a functional state between quiescence and active proliferation. Here, we asked whether protein flux rates are altered in muscle distant from acute local myotoxic injury and how they compare to changes in gene expression from the same tissue. Broad and significant alterations in protein turnover were observed across the proteome in the limb contralateral to injury during the first 10 days after. Interestingly, mRNA changes had almost no correlation with directly measured protein turnover rates. In summary, we show consistent and striking changes in protein flux rates in muscle tissue contralateral to myotoxic injury, with no correlation between changes in mRNA levels and protein synthesis rates. This work motivates further investigation of the mechanisms, including potential neurologic factors, responsible for this distant effect.
2024-04-30 | PXD051860 | JPOST Repository
Project description:Common acute injuries to skeletal muscle can lead to significant pain and disability. The current therapeutic approaches for treating muscle injuries are dependent on the clinical severity but not on the type of injury. The aim of this study was to compare the molecular events accompanying the degeneration and repair phases of contraction- and trauma-induced muscle injuries by applying DNA microarray methodology to two well-characterized mouse models of skeletal muscle injury, i.e., eccentric contraction-induced injury (CI) and traumatic injury induced by freezing (FI). Histopathological evaluation and measurements of muscle strength were accompanied by analyses of expression for 12,488 known genes at four time points ranging from 6 hours to 7 days post-injury. Real-time RT-PCR was used to confirm some of the gene expression temporal profiles. While both types of injury cause early induction of transcription, myogenic, and stress-responsive factors, they also induce injury type-specific gene expression profiles. CI only activates a set of genes associated with the protection and repair of protein and structural integrity while FI activates gene sets which result in extensive inflammatory responses, tissue remodeling, angiogenesis, and myofibre and extracellular matrix synthesis. This study identified genes that are candidates for therapeutic manipulation following two disparate types of muscle injury. Keywords: time course, comparative genomic hybridization
2006-12-31 | GSE5413 | GEO
Project description:Repetitive mild traumatic brain injuries (rmTBI) sustained within a window of vulnerability can result in long term cognitive deficits, depression, and eventual neurodegeneration associated with tau pathology, amyloid beta plaques, gliosis, and neuronal and functional loss. However, we have limited understanding of how successive injuries affect the brain to result in these devastating long-term consequences. In the current study, we addressed the question of how repeated injuries affect the brain in the acute phase of injury (<24hr) by exposing the 3xTg-AD mouse model of tau and amyloid beta pathology to successive (1x, 3x, 5x) once-daily weight drop closed-head injuries and quantifying transcription at 30min, 4hr, and 24hr after each injury.
2024-05-17 | GSE226838 | GEO
Project description:The lamprey is a vertebrate that, unlike mammals, achieves spontaneous recovery after spinal cord transection. Despite anatomical, physiological, and behavioral data on spinal cord regeneration in lamprey, the molecular mechanisms underlying this capacity are largely unknown. To address this, we used RNA-Seq to obtain transcriptional profiles from uninjured animals and at 10 time points ranging from 6 hours to 12 weeks post injury. Overall, 4208 (spinal cord) and 3788 (brain) transcripts are differentially expressed (DE). Complex intraspinal and supraspinal responses were induced acutely and occurred even at chronic phases of recovery. Leveraging functional data for mammalian homologs of DE genes (via Enrichr) permitted identification of enriched conserved genes and pathways. These included genes and pathways induced after mammalian peripheral nerve injury, such as those associated with regeneration, immune function, cell growth, proliferation and cell death. For example, ATF3, a transcription factor implicated in mammalian peripheral nerve regeneration, is highly expressed and enriched in lamprey spinal cord and brain after SCI. Other homologs of regeneration-associated genes that are differentially expressed after SCI include members of the WNT, HDAC, SOX, SMAD, KLF, and JUN families. This study provides the first comprehensive view of transcriptional responses during successful anatomical and functional recovery from spinal cord injury in lamprey, and reveals unexpectedly large changes in transcription in the brain, which is quite distant from the spinal lesion site. Gene expression patterns associated with functional recovery in lamprey may be useful in guiding studies aimed at modulating mammalian responses to SCI.
2018-03-03 | GSE95686 | GEO
Project description:The proteasome maintains protein quality during aging and disease. Challenges to proteasome function can be compensated by local proteasome stress responses. However, whereas proteasome stress is also sensed systemically is unknown. In Drosophila , we find that proteasome stress in skeletal muscle non-autonomously promotes the degradation of proteasome substrates in distant tissues during aging. Several muscle-secreted factors (myokines) are upregulated by proteasomal stress via C/EBP transcription factors, including the amylase Amyrel, which increases the circulating levels of the disaccharide maltose. Muscle-specific Amyrel overexpression promotes the degradation of proteasome substrates in the aging brain and retina via the transcriptional induction of chaperones and proteases. Conversely, RNAi for maltose transporters worsens proteostasis and reduces the expression of Amyrel-induced genes in the brain. Moreover, maltose preserves protein quality in cell culture and human cortical brain organoids challenged by thermal stress. Thus, proteasome stress in skeletal muscle mounts a systemic adaptive response via amylase/maltose signaling.
2021-02-12 | GSE149798 | GEO