Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA273550 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Chronic kidney disease (CKD) is the gradual, asymptomatic loss of kidney function and current tests only identify it when significant loss has already happened. Using RNA sequencing in a mouse model of folic acid (FA) induced nephropathy, here we report the identification of 10 genes that track kidney fibrosis development, the common pathological finding in CKD patients. The gene expression of all 10 candidates was confirmed to be significantly high (~ 10-150 fold) in three well-established and mechanistically distinct mouse models of kidney fibrosis. Protein expression was also high in the FA model as well as patients with biopsy-proven kidney fibrosis. The specificity of these 10 candidates for kidney fibrosis was demonstrated by showing a very modest (~ 2-5 fold) increase in the mouse models of acute kidney injury as well as following liver fibrosis in mice and humans. Using targeted selected reaction monitoring mass spectrometry (SRM-MS) we found that 3 out of 10, cadherin 11 (CDH11), mannose receptor C1 (MRC1), phospholipid transfer protein (PLTP), are detectable in human urine. Furthermore, the levels of CDH11 and MRC1 are able to distinguish patients with chronic kidney disease from healthy individuals (n = 78, p<0.01). In summary, we report the identification of CDH11 and MRC1 as novel non-invasive biomarkers of CKD. mRNA sequencing of mouse kidney before and at various time points (1,2,3,7 & 14 days) after intraperitoneal treatment with folic acid.
2015-10-23 | E-GEOD-65267 | biostudies-arrayexpress
Project description:Chronic kidney disease (CKD) is the gradual, asymptomatic loss of kidney function and current tests only identify it when significant loss has already happened. Using RNA sequencing in a mouse model of folic acid (FA) induced nephropathy, here we report the identification of 10 genes that track kidney fibrosis development, the common pathological finding in CKD patients. The gene expression of all 10 candidates was confirmed to be significantly high (~ 10-150 fold) in three well-established and mechanistically distinct mouse models of kidney fibrosis. Protein expression was also high in the FA model as well as patients with biopsy-proven kidney fibrosis. The specificity of these 10 candidates for kidney fibrosis was demonstrated by showing a very modest (~ 2-5 fold) increase in the mouse models of acute kidney injury as well as following liver fibrosis in mice and humans. Using targeted selected reaction monitoring mass spectrometry (SRM-MS) we found that 3 out of 10, cadherin 11 (CDH11), mannose receptor C1 (MRC1), phospholipid transfer protein (PLTP), are detectable in human urine. Furthermore, the levels of CDH11 and MRC1 are able to distinguish patients with chronic kidney disease from healthy individuals (n = 78, p<0.01). In summary, we report the identification of CDH11 and MRC1 as novel non-invasive biomarkers of CKD.
2015-10-23 | GSE65267 | GEO
Project description:Curing treatment for HBV infection is yet unavailable, mainly due to unmet gaps in current understanding of the details about HBV-host interaction. By quantitatively assessing HBV-induced global changes in host transcriptome, translatome and proteome, we identified multiple previously unknown transcriptional and translational events that HBV orchestrated to remodel host proteostasis networks and afford micro-environments essential for HBV proliferation and persistence.By delineating novel drug targets and biomarkers in HBV-host interaction, multi-omics interrogation may facilitate the development of next-generation therapeutics or diagnostics against HBV infection and the related maladies.
2021-03-06 | GSE135860 | GEO
Project description:Next generation sequencing in a rat model of diabetic nephropathy was employed to study in depth the pathogenic alterations involved in progressive diabetic kidney damage. We employed the obese, diabetic ZS rat, a model that develops renal failure and fibrosis, the hallmarks of human disease. We then used RNA-seq to examine in a comprehensive manner the combined effects of renal cells and infiltrating inflammatory cells acting as a pathophysiological unit. 12 samples (4 independent samples for each of 3 groups, 1 control group)
2014-02-06 | E-GEOD-44375 | biostudies-arrayexpress
Project description:Next generation sequencing in a rat model of diabetic nephropathy was employed to study in depth the pathogenic alterations involved in progressive diabetic kidney damage. We employed the obese, diabetic ZS rat, a model that develops renal failure and fibrosis, the hallmarks of human disease. We then used RNA-seq to examine in a comprehensive manner the combined effects of renal cells and infiltrating inflammatory cells acting as a pathophysiological unit.
2014-02-06 | GSE44375 | GEO
Project description:Despite recent advances in genomics, the identification of genes underlying complex diseases remains challenging. Inbred rat strains offer well-established experimental models to support the identification of susceptibility genes for diseases such as kidney damage associated with elevated blood pressure or hypertension. Here, we combined quantitative trait locus (QTL) mapping in two contrasting inbred rat strains with targeted next generation sequencing (NGS), compartment-specific transcriptome sequencing (RNA-Seq), and phenotype directed follow-up translational analysis.
2018-08-11 | GSE102546 | GEO
Project description:Interstitial fibrosis and tubular atrophy (IF/TA) after kidney transplantation causes chronic deterioration of graft function. IF/TA can be diagnosed by graft biopsy; however, non-invasive diagnostic methods are unavailable. In this study, we identified IF/TA-related differentially expressed genes (DEGs) through next-generation sequencing using peripheral blood mononuclear cells (PBMCs) PBMC samples from kidney transplantation recipients under standard immunosuppressive therapy (tacrolimus/mycophenolate mofetil or mycophenolate sodium/steroid) and diagnosed as IF/TA (n = 41) or normal (controls; n = 41) at their 1-year protocol biopsy were recruited between January 2020 and August 2020.
2023-08-30 | GSE218048 | GEO
Project description:Chronic kidney disease (CKD) is characterized by sustained inflammation and progressive fibrosis, however therapies to slow CKD progression are limited. Histone lysine crotonylation (Kcr) as a novel post-translational modification is widespread as acetylation (Kac), but its roles in CKD are largely unknown. In the study, we firstly reported that the nuclear histone Kcr in tubular epithelial cells was significantly elevated in fibrotic kidney of patients and mice, which was positively correlated with the progression of disease. Interestingly, abnormal increase of histone 3 lysine 9 crotonylation (H3K9cr) in kidneys of unilateral ureteric obstruction (UUO) and folic acid nephropathy (FAN) was completely different to the stable expression of H3K9ac, indicating that H3K9cr may exert extraordinary functions in kidney fibrosis. By screening these crotonylated/acetylated factors, crotonyl-CoA-producing enzyme ACSS2 (acyl-CoA synthetase short chain family member 2) remarkably promoted H3K9cr without influencing H3K9ac to trigger proinflammatory cytokine IL-1β transcription. Furthermore, genetic and pharmacologic inhibition of ACSS2 both attenuated kidney injury and fibrosis, as well as suppressed H3K9cr-mediated IL-1β expression, which thus to alleviate IL-1β-dependent macrophage activation and tubular cell senescence. Collectively, our finding uncovers that H3K9cr plays a critical, previously unrecognized role in kidney fibrosis, where ACSS2 represents an attractive target for strategies that aim to slow fibrotic kidney disease progression
2024-02-08 | GSE253032 | GEO
Project description:Chronic kidney disease (CKD) is characterized by sustained inflammation and progressive fibrosis, however therapies to slow CKD progression are limited. Histone lysine crotonylation (Kcr) as a novel post-translational modification is widespread as acetylation (Kac), but its roles in CKD are largely unknown. In the study, we firstly reported that the nuclear histone Kcr in tubular epithelial cells was significantly elevated in fibrotic kidney of patients and mice, which was positively correlated with the progression of disease. Interestingly, abnormal increase of histone 3 lysine 9 crotonylation (H3K9cr) in kidneys of unilateral ureteric obstruction (UUO) and folic acid nephropathy (FAN) was completely different to the stable expression of H3K9ac, indicating that H3K9cr may exert extraordinary functions in kidney fibrosis. By screening these crotonylated/acetylated factors, crotonyl-CoA-producing enzyme ACSS2 (acyl-CoA synthetase short chain family member 2) remarkably promoted H3K9cr without influencing H3K9ac to trigger proinflammatory cytokine IL-1β transcription. Furthermore, genetic and pharmacologic inhibition of ACSS2 both attenuated kidney injury and fibrosis, as well as suppressed H3K9cr-mediated IL-1β expression, which thus to alleviate IL-1β-dependent macrophage activation and tubular cell senescence. Collectively, our finding uncovers that H3K9cr plays a critical, previously unrecognized role in kidney fibrosis, where ACSS2 represents an attractive target for strategies that aim to slow fibrotic kidney disease progression
2024-02-08 | GSE245390 | GEO
Project description:Protein L-isoaspartyl/D-aspartyl Methyltransferase (PCMT1) plays a pivotal role in repairing a spontaneous post-translational modification (PTM) of L-isoaspartyl residues resulted from asparagine deamidation or aspartate isomerization. This PTM is particularly important for extracellular matrix (ECM) proteins because their low turnover rate and are susceptible to factors that could accelerate such modification. Therefore, it becomes imperative to comprehensively investigate the impact of PCMT1 on ECM homeostasis and its associated pathological alterations. In this study, we revealed that secreted PCMT1 repairs the isoaspartyl residues of the TGFBR2 protein on the cell membrane to suppress TGF-β1/Smad pathway. Through this novel PTM regulation, PCMT1 played essential roles in combating renal fibrosis, as lack of PCMT1 worsened tubular injury, collagen deposition, myofibroblast activation, and macrophage infiltration in total kidney and tubular contexts in a mouse model of chronic kidney disease. Moreover, PCMT1 level decreased in fibrotic kidney tissues and inversely related to kidney function in mice and in humans. Our study highlights the important function of PCMT1 in modifying proteins in the extracellular space and identified a novel role of PCMT1 in regulating TGF-β1 pathway in renal fibrosis. This study holds the potential of innovative therapeutic avenue for the mitigation of renal fibrosis.
2024-01-01 | GSE248435 | GEO