The significance of Pax2 expression in the ureter epithelium of children with vesicoureteric reflux

Hum Pathol. 2015 Jul;46(7):963-70. doi: 10.1016/j.humpath.2015.01.007. Epub 2015 Jan 16.

Abstract

Vesicoureteral reflux (VUR) is the retrograde passage of urine from the bladder to the urinary tract; this leads to renal scarring and end-stage renal disease in children. Pax2 is a nuclear transcription factor that is involved in urinary system development. We measured the expression of Pax2 in the ureters of 47 patients with VUR. The messenger RNA expression and the protein level of Pax2 were significantly increased in patients with VUR, suggesting a correlation with VUR. Further studies demonstrated that Pax2 was hypomethylated, and Dnmt3a messenger RNA expression was significantly lower than in the control group. We speculate that the low level of Dnmt2a might decrease PAX2 gene methylation and up-regulate the Pax2 protein. The high level of Pax2 might be related to cellular apoptosis and functional lesions in ureters. In conclusion, our results revealed that the level of Pax2 is correlated with VUR; thus, Pax2 represents a possible target for VUR therapy.

Keywords: DNA methylation; Epigenetics; Immunohistochemistry; Pax2; Pediatrics; Vesicoureteral reflux.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Biomarkers / analysis
  • Child
  • Child, Preschool
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation
  • Epigenesis, Genetic
  • Female
  • Humans
  • Infant
  • Male
  • PAX2 Transcription Factor / analysis*
  • PAX2 Transcription Factor / genetics
  • RNA, Messenger / analysis
  • Up-Regulation
  • Ureter / chemistry*
  • Ureter / pathology
  • Urothelium / chemistry*
  • Urothelium / pathology
  • Vesico-Ureteral Reflux / diagnosis
  • Vesico-Ureteral Reflux / genetics
  • Vesico-Ureteral Reflux / metabolism*

Substances

  • Biomarkers
  • PAX2 Transcription Factor
  • PAX2 protein, human
  • RNA, Messenger
  • DNA (Cytosine-5-)-Methyltransferases
  • TRDMT1 protein, human