Molecular basis of renal adaptation in a murine model of congenital obstructive nephropathy

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 k...

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Published in:PloS one 2013-09, Vol.8 (9), p.e72762-e72762
Main Authors: Becknell, Brian, Carpenter, Ashley R, Allen, Jordan L, Wilhide, Michael E, Ingraham, Susan E, Hains, David S, McHugh, Kirk M
Format: Article
Language:English
Subjects:
Adaptation
Animal models
Animals
Biology
Biomarkers
Borides
Children
Chronic kidney failure
Congenital diseases
Disease Models, Animal
Gender
Gene expression
Genes
Genetic disorders
Hydronephrosis - genetics
Hydronephrosis - metabolism
Immunohistochemistry
Injuries
Kidney - metabolism
Kidney - physiopathology
Kidney diseases
Kidney Diseases - genetics
Kidney Diseases - metabolism
Kidney transplantation
Kidneys
Laboratory animals
Male
Medicine
Metabolism
Mice
Mice, Knockout
Nephrology
Nephropathy
Pathophysiology
Pediatrics
Polymerase Chain Reaction
Rodents
Signaling
Stem cells
Steroid hormones
Studies
Transcription
Urology
Urothelium
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cited_by cdi_FETCH-LOGICAL-c692t-c7881707807a3e91813df471bed02282913f73087e1466d437cc8e438d6031713
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container_issue 9
container_start_page e72762
container_title PloS one
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creator Becknell, Brian
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Allen, Jordan L
Wilhide, Michael E
Ingraham, Susan E
Hains, David S
McHugh, Kirk M
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 Ngal(high) versus Ngal(low) 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.
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subjects Adaptation
Animal models
Animals
Biology
Biomarkers
Borides
Children
Chronic kidney failure
Congenital diseases
Disease Models, Animal
Gender
Gene expression
Genes
Genetic disorders
Hydronephrosis - genetics
Hydronephrosis - metabolism
Immunohistochemistry
Injuries
Kidney - metabolism
Kidney - physiopathology
Kidney diseases
Kidney Diseases - genetics
Kidney Diseases - metabolism
Kidney transplantation
Kidneys
Laboratory animals
Male
Medicine
Metabolism
Mice
Mice, Knockout
Nephrology
Nephropathy
Pathophysiology
Pediatrics
Polymerase Chain Reaction
Rodents
Signaling
Stem cells
Steroid hormones
Studies
Transcription
Urology
Urothelium
title Molecular basis of renal adaptation in a murine model of congenital obstructive nephropathy
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