Proteomic Insights into Aprotinin’s Immunomodulatory Effects in Attenuating Renal Fibrosis in a Unilateral Ureteral Obstruction Model
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Qinyuan Deng
PROVIDER: PXD063655 | iProX | Sat May 03 00:00:00 GMT+01:00 2025
REPOSITORIES: iProX
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Project description:Congenital obstructive nephropathy (CON) is the leading cause of pediatric chronic kidney diseases with high morbidity and mortality.To identify differentially expressed genes, microarray analysis was performed using the unilateral ureteral obstruction (UUO)-induced neonatal rat model of CON.
2017-01-26 | E-MTAB-4984 | biostudies-arrayexpress
Project description:Congenital obstructive nephropathy is a common cause of chronic kidney disease and a leading indication for renal transplant in children. The cellular and molecular responses of the kidney to congenital obstruction are incompletely characterized. In this study, we evaluated global transcription in kidneys with graded hydronephrosis in the megabladder (mgb-/-) mouse to better understand the pathophysiology of congenital obstructive nephropathy. Three primary pathways associated with kidney remodeling/repair were induced in mgb-/- kidneys independent of the degree of hydronephrosis. These pathways included retinoid signaling, steroid hormone metabolism, and renal response to injury. Urothelial proliferation and the expression of genes with roles in the integrity and maintenance of the renal urothelium were selectively increased in mgb-/- kidneys. Ngal/Lcn2, a marker of acute kidney injury, was elevated in 36% of kidneys with higher grades of hydronephrosis. Evaluation of Ngalhigh versus Ngallow kidneys identified the expression of several novel candidate markers of renal injury. This study indicates that the development of progressive hydronephrosis in mgb-/- mice results in renal adaptation that includes significant changes in the morphology and potential functionality of the renal urothelium. These observations will permit the development of novel biomarkers and therapeutic approaches to progressive renal injury in the context of congenital obstruction. Gene expression was measured in control, mild, moderate and severely hydronephrotic megabladder mouse kidneys. A total of 6 control kidneys were compared to 18 mutant kidneys from age-matched male animals.
2013-06-18 | E-GEOD-48041 | biostudies-arrayexpress
Project description:Chronic kidney disease (CKD) is a burden for Public Health and concerns millions of individuals worldwide. Independently of the cause, CKD is secondary to the replacement of functional renal tissue by extra-cellular matrix proteins (i.e fibrosis) that progressively impairs kidney function. The pathophysiological pathways that control the development of renal fibrosis are common to most of the nephropathies involving native kidneys or kidney grafts. Unfortunately, very few treatments are available to stop renal fibrosis and most of the therapeutic strategies are often barely able to slow down the progression of fibrogenesis in native kidneys. Therefore, it is mandatory to discover new therapeutic pathways to stop renal fibrosis. Our objective is to study new pathways involved in renal fibrosis. We thus decided to use the model of Unilateral Ureteral renal Obstruction in mice, a fast and reproducible experimental model of renal fibrosis. We studied renal fibrosis using experimental model of ureteral unilateral obstruction in mice, which was performed by complete ligation of the left ureter. The control lateral right kidney served as internal control.
2013-02-10 | E-GEOD-38117 | biostudies-arrayexpress
Project description:Congenital obstructive nephropathy is a common cause of chronic kidney disease and a leading indication for renal transplant in children. The cellular and molecular responses of the kidney to congenital obstruction are incompletely characterized. In this study, we evaluated global transcription in kidneys with graded hydronephrosis in the megabladder (mgb-/-) mouse to better understand the pathophysiology of congenital obstructive nephropathy. Three primary pathways associated with kidney remodeling/repair were induced in mgb-/- kidneys independent of the degree of hydronephrosis. These pathways included retinoid signaling, steroid hormone metabolism, and renal response to injury. Urothelial proliferation and the expression of genes with roles in the integrity and maintenance of the renal urothelium were selectively increased in mgb-/- kidneys. Ngal/Lcn2, a marker of acute kidney injury, was elevated in 36% of kidneys with higher grades of hydronephrosis. Evaluation of Ngalhigh versus Ngallow kidneys identified the expression of several novel candidate markers of renal injury. This study indicates that the development of progressive hydronephrosis in mgb-/- mice results in renal adaptation that includes significant changes in the morphology and potential functionality of the renal urothelium. These observations will permit the development of novel biomarkers and therapeutic approaches to progressive renal injury in the context of congenital obstruction.
2013-06-18 | GSE48041 | GEO
Project description:The kidney has limited capacity to regenerate following injury and preferentially repairs chronic injury with secreted extracellular matrix proteins. This can be a progressive process with functioning kidney tissue being replaced detrimentally with fibrotic scar tissue, ultimately leading to kidney failure. Using the reversible unilateral ureteric obstruction model, a model of reversable injury, we describe the transcriptomic changes that occur during obstructive renal injury and subsequent repair.
2020-09-27 | GSE145053 | GEO
Project description:Chronic kidney disease (CKD) remains a tremendous and growing burden on the healthcare system and new therapies are needed to prevent or slow disease progression. Metabolic dysregulation and mitochondrial dysfunction are important features of acute and chronic tissue injury across species, and human genetics and preclinical data suggest that the master metabolic regulator 5'-adenosine monophosphate activated protein kinase (AMPK) may be an effective therapeutic target for CKD. Merck has recently disclosed a pan-AMPK activator MK-8722 which was shown to have beneficial effects on metabolic parameters in preclinical models. In this study we investigate the effects of MK-8722 in a progressive model of diabetic nephropathy to determine whether activation of AMPK would be of therapeutic benefit. We find that MK-8722 administration in a therapeutic paradigm is profoundly reno-protective. We provide evidence that the therapeutic effects may be mediated by modulation of renal mitochondrial quality control as well as by attenuating fibrotic and lipotoxic mechanisms in kidney cells. These data further validate the concept that targeting metabolic dysregulation in CKD could be a potential therapeutic approach.
2019-07-25 | GSE134804 | GEO
Project description:Congenital obstructive nephropathy (CON) is the leading cause of chronic kidney disease (CKD) in children. CON is a complex disease process involving pathological changes in kidney development and function that occur as a result of obstructed antegrade urine flow beginning in utero. The megabladder (mgb-/-) mouse is an animal model of CON that develops kidney disease secondary to a bladder-specific defect in smooth muscle development. Expression levels of specific microRNAs were compared by microarray analysis on the Agilent platform and by quantitative PCR (qPCR) of kidney samples from wild type and mgb-/- mice.
2016-07-08 | GSE70879 | GEO
Project description:Introduction It is necessary to study the time series of obstructive nephropathy because of different pathophysiological changes in different stages of obstructive nephropathy. Methods In order to recognize the dynamic molecular changes of obstructive nephropathy, this study applied multi-omics ways to evaluate the mRNA and metabolite in different stage of obstructive nephropathy. Results Based on Gene Ontology (GO) and KEGG pathway analyses of transcriptome and metabolism, we defined specific pathways and persistent pathways in the early, middle, and late stages of obstructive nephropathy. adipocytokine signaling pathway, PPAR signaling pathway, JAK-STAT signaling pathway and all types of amino acid metabolism receive the most attention. Conclusion Through this approach, it was discovered that targeting specific molecules, proteins, kinases and critical pathways could be a promising approach for treating obstructive nephropathy.
2025-08-10 | GSE304946 | GEO
Project description:Chronic kidney disease (CKD) is a burden for Public Health and concerns millions of individuals worldwide. Independently of the cause, CKD is secondary to the replacement of functional renal tissue by extra-cellular matrix proteins (i.e fibrosis) that progressively impairs kidney function. The pathophysiological pathways that control the development of renal fibrosis are common to most of the nephropathies involving native kidneys or kidney grafts. Unfortunately, very few treatments are available to stop renal fibrosis and most of the therapeutic strategies are often barely able to slow down the progression of fibrogenesis in native kidneys. Therefore, it is mandatory to discover new therapeutic pathways to stop renal fibrosis. Our objective is to study new pathways involved in renal fibrosis. We thus decided to use the model of Unilateral Ureteral renal Obstruction in mice, a fast and reproducible experimental model of renal fibrosis.
2013-02-10 | GSE38117 | GEO
Project description:Acute kidney injury(AKI) is associated with an increased risk of chronic kidney disease(CKD). There is still a lack of effective prevention for AKI-CKD transition. In the present study, we simultaneously explored the contribution of GSDMD and GSDME in folic acid (FA)-induced nephropathy, a model mimicking the essential components of the AKI-CKD transition. We found that blockage of both GSDMD and GSDME-mediated pyroptosis could have accumulative protection against FA-induced AKI-CKD transition. GSDME-mediated pyroptosis played a crucial role in tubular cell damage. GSDMD could exert important functions in infiltration of inflammatory cells and NETs formation. Pyroptotic tubular cells triggered NETs generation and macrophage polarization. NETs promoted macrophage-to-myofibroblast transition. Our results illustrated the orchestration of GSDMD and GSDME in AKI-CKD transition, providing new insights into the molecular mechanism for the clinical dilemma.
2024-10-31 | GSE245446 | GEO