Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Tracking the molecular patterns of a common response across tissues in murine sepsis to refine treatment strategies

ABSTRACT: Transcriptional effects in liver, lung, spleen and blood samples from mice challenged to Sham and Sepsis by Peritoneal Contamination and Infection (PCI) were monitored after 6 and 24 hours 4 Tissues x 2 Time Resolved Treatment Groups x 4 Replicates, 4 Tissues x Sham Control x 3 Replicates

ORGANISM(S): Mus musculus

SUBMITTER: S. Lambeck

PROVIDER: E-GEOD-23767 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Cyclophosphamide (CPAm) is a widely used chemotherapeutic agent that exhibits potent anti-cancer properties but is often associated with debilitating side effects. Despite its efficacy, the management of CPAm-induced toxicities remains a significant clinical challenge. There has been growing interest in exploring complementary and alternative therapies to mitigate these adverse effects in recent years, and this may be a chance for the earthworm-derived preparation, Venetin 1. Its rich composition of bioactive compounds has demonstrated promising pharmacological properties, including anti-inflammatory, antioxidant, and immunomodulatory effects. These properties suggest its potential to counteract the various systemic toxicities induced by CP. To investigate the effect of Venetin 1 on cyclophosphamide-induced toxicity, we conducted a comprehensive study. Mice were administered CPAm for four days, followed by the earthworm preparation in two doses (50 mg/kg and 100 mg/kg b.w). Importantly, the preparation did not cause any side effects in all mice, ensuring the safety of the intervention. We then determined global changes in the proteome using proteomics and quantitative SWATH-MS analysis, a robust and reliable method. This allowed us to identify up- and downregulated proteins in each studied group, providing valuable insights into the mechanism of action of Venetin 1. According to the obtained results, Venetin 1 significantly affected the proteome of mouse lung tissue. It was possible to determine quantitative changes for 400 proteins, and the analysis after administration of Venetin 1 showed a change in the global proteomic profile from upregulated to down-regulated. The stimulating properties of the preparation concerning the complement system have also been confirmed in a separate validation experiment. It has been shown that Venetin 1 has the potential to eliminate the toxic effect of cyclophosphamide in lung tissue. It also initiates regenerative processes, inhibits inflammatory processes, supports autophagy and stimulates the immune system. Further research is required to understand and to fully describe the effects of Venetin 1 .

Project description:Acute kidney injury (AKI) is associated with an abrupt loss of kidney function that results in significant morbidity and mortality. Considerable effort has focused around the identification of diagnostic biomarkers and the analysis of molecular events. Most studies have adopted organ-wide approaches that do not fully capture the interplay among different cell types in the pathophysiology of AKI. To extend our understanding of molecular and cellular events in AKI, we developed a mouse line that enables the identification of translational profiles in specific cell types by CRE recombinase-dependent activation of an eGFP-tagged L10a ribosomal protein subunit, and consequently, translating ribosome affinity purification (TRAP) of mRNA populations. By utilizing cell-type specific CRE-driver lines, in this study we identify distinct cellular responses in an ischemia reperfusion injury (IRI) model of AKI. Cell-specific translational expression profiles were uncovered 24 hours after IRI from four populations enriched for distinct anatomical and cellular subgroups: nephron, interstitial cell populations, vascular endothelium, and macrophages/monocytes by Affymetrix microarray. A construct containing the CAGGS promoter driving eGFP-L10a, with a loxP-site flanked triple SV40 polyA cassette between promoter and eGFP-L10a cassette was targeted into the ubiquitously active Rosa26 locus. The upstream polyA cassette is designed to block activity of the downstream eGFP-L10a cassette. CRE-dependent removal of this transcriptional block activates eGFP::L10a production within the CRE-producing cell, and all of its descendants. Mice carrying the conditional eGFP-L10a allele, referred to as L10a, were maintained in a homozygous state. L10a mice were crossed to four CRE strains to activate eGFP::L10a expression in four predominantly non-overlapping cellular compartments in the kidney. A Six2-Tet-GFP::CRE allele is active exclusively within nephron progenitors; consequently, historical labeling results in eGFP::L10a expression throughout the main body of the nephron. A Foxd1-GFP::CRE allele is active in the progenitors of many of the interstitial cell lineages including those generating mesangial and non-glomerular pericytes. In addition, Foxd1 is normally expressed in podocytes. Cdh5-CRE is reported to be active throughout the vascular endothelium, and finally, Lyz2-CRE specifically labels cells of the myeloid lineage, notably macrophages, monocytes and dendritic cells. Mice carrying any CRE allele and the L10a allele are designated generically CRE-L10a. six2-L10a, foxd1-L10a, cdh5-L10a and lyz2-L10a denote specifically mice that are compound heterozygotes for the indicated CRE driver and L10a. CRE-L10a, L10a heterozygous littermates without CRE allele, C57BL/6 wild type mice were subjected to renal bilateral warm ischemia 28 minutes followed by 24-hour reperfusion when the kidney TRAP RNA and total RNA were isolated and subjected to Affymetrix microarray. Biological triplicates for each CRE-L10a line underwent no Surgery; sham Surgery and IRI treatment.

Dataset Information

Tracking the molecular patterns of a common response across tissues in murine sepsis to refine treatment strategies

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets