Molecular Basis of Renal Adaptation in a Murine Model of Congenital Obstructive Nephropathy

Brian Becknell, Ashley R. Carpenter, Jordan L. Allen, Michael E. Wilhide, Susan E. Ingraham, David Hains, Kirk M. McHugh

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere72762
JournalPloS one
Volume8
Issue number9
DOIs
StatePublished - Sep 4 2013

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Steroid hormones
Transplants
Retinoids
Biomarkers
Transcription
kidney diseases
Metabolism
Repair
Genes
animal models
kidneys
Kidney
Hydronephrosis
Urothelium
Wounds and Injuries
steroid metabolism
hormone metabolism
kidney transplant
retinoids
mice

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Becknell, B., Carpenter, A. R., Allen, J. L., Wilhide, M. E., Ingraham, S. E., Hains, D., & McHugh, K. M. (2013). Molecular Basis of Renal Adaptation in a Murine Model of Congenital Obstructive Nephropathy. PloS one, 8(9), [e72762]. https://doi.org/10.1371/journal.pone.0072762

Molecular Basis of Renal Adaptation in a Murine Model of Congenital Obstructive Nephropathy. / Becknell, Brian; Carpenter, Ashley R.; Allen, Jordan L.; Wilhide, Michael E.; Ingraham, Susan E.; Hains, David; McHugh, Kirk M.

In: PloS one, Vol. 8, No. 9, e72762, 04.09.2013.

Research output: Contribution to journalArticle

Becknell, B, Carpenter, AR, Allen, JL, Wilhide, ME, Ingraham, SE, Hains, D & McHugh, KM 2013, 'Molecular Basis of Renal Adaptation in a Murine Model of Congenital Obstructive Nephropathy', PloS one, vol. 8, no. 9, e72762. https://doi.org/10.1371/journal.pone.0072762
Becknell, Brian ; Carpenter, Ashley R. ; Allen, Jordan L. ; Wilhide, Michael E. ; Ingraham, Susan E. ; Hains, David ; McHugh, Kirk M. / Molecular Basis of Renal Adaptation in a Murine Model of Congenital Obstructive Nephropathy. In: PloS one. 2013 ; Vol. 8, No. 9.
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