Proteomic Insights into Aprotinin’s Immunomodulatory Effects in Attenuating Renal Fibrosis in a Unilateral Ureteral Obstruction Model
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ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Qinyuan Deng
PROVIDER: PXD063655 | iProX | Sat May 03 00:00:00 BST 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.
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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.
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