2,8-Dihydroxyadenine Nephrolithiasis Induces Developmental Stage-specific Alterations in Gene Expression in Mouse Kidney

Jianmin Chen, Yanping Chen, Stephanie Capizzi, Min Yang, Li Deng, Sharon B. Bledsoe, Andrew P. Evan, Jay A. Tischfield, Amrik Sahota

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objectives: To identify factors that may be crucial for the initiation and progression of stone-induced injury in the developing mouse kidney by a prospective observational study using microarray analysis. Kidney stone diseases are common in premature infants, but the underlying molecular and cellular mechanisms are not fully defined. Methods: Mice with adenine phosphoribosyltransferase deficiency develop 2,8-dihydroxyadenine (DHA) nephrolithiasis. The gene expression changes between Aprt-/- and Aprt+/+ kidneys from newborn and adult mice were compared using Affymetrix gene chips. Targets of interest were further analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry. Results: We identified a set of genes that were differentially expressed in the developing kidney in response to DHA-induced injury. In 1-week-old Aprt-/- mice, the expression of Sprr2f and Clu was highly augmented and that of Egf was significantly decreased. We also observed that maturation-related gene expression changes were delayed in developing Aprt-/- kidneys, and immature Aprt-/- kidneys contained large numbers of intercalated cells that were blocked from terminal differentiation. Conclusions: This study presents a comprehensive picture of the transcriptional changes induced by DHA stone injury in the developing mouse kidney. Our findings help explain growth impairment in kidneys subject to injury during the early stages of development.

Original languageEnglish (US)
Pages (from-to)914-922
Number of pages9
JournalUrology
Volume75
Issue number4
DOIs
StatePublished - Apr 1 2010

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Nephrolithiasis
Kidney
Gene Expression
Wounds and Injuries
Kidney Calculi
Kidney Diseases
Microarray Analysis
2,8-dihydroxyadenine
Oligonucleotide Array Sequence Analysis
Premature Infants
Observational Studies
Real-Time Polymerase Chain Reaction
Cell Count
Immunohistochemistry
Newborn Infant
Prospective Studies
Growth
Genes

ASJC Scopus subject areas

  • Urology

Cite this

2,8-Dihydroxyadenine Nephrolithiasis Induces Developmental Stage-specific Alterations in Gene Expression in Mouse Kidney. / Chen, Jianmin; Chen, Yanping; Capizzi, Stephanie; Yang, Min; Deng, Li; Bledsoe, Sharon B.; Evan, Andrew P.; Tischfield, Jay A.; Sahota, Amrik.

In: Urology, Vol. 75, No. 4, 01.04.2010, p. 914-922.

Research output: Contribution to journalArticle

Chen, J, Chen, Y, Capizzi, S, Yang, M, Deng, L, Bledsoe, SB, Evan, AP, Tischfield, JA & Sahota, A 2010, '2,8-Dihydroxyadenine Nephrolithiasis Induces Developmental Stage-specific Alterations in Gene Expression in Mouse Kidney', Urology, vol. 75, no. 4, pp. 914-922. https://doi.org/10.1016/j.urology.2009.10.031
Chen, Jianmin ; Chen, Yanping ; Capizzi, Stephanie ; Yang, Min ; Deng, Li ; Bledsoe, Sharon B. ; Evan, Andrew P. ; Tischfield, Jay A. ; Sahota, Amrik. / 2,8-Dihydroxyadenine Nephrolithiasis Induces Developmental Stage-specific Alterations in Gene Expression in Mouse Kidney. In: Urology. 2010 ; Vol. 75, No. 4. pp. 914-922.
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