Up-regulation of tissue and urinary uroplakin mrnas in congenital vesicoureteral reflux

Vesicoureteral Reflux and Pyelonephritis: Risk Factors, Prevalence and Treatment Approaches
  • Tatsuhiro Yoshiki
  • ,
  • Tatsuhiro Yoshiki
  • ,
  • Hideaki Iwaki
  • ,
  • Ken Ichi Kobayashi
  • ,
  • Susumu Kageyama
  • ,
  • Hiromi Ii
  • ,
  • Akihiro Kawauchi


© 2015 Nova Science Publishers, Inc. Aim: Uroplakins (UPs) are urothelium-specific transmembrane proteins consisting of the following four families: Uroplakin Ia (UPIa), uroplakin Ib (UPIb), uroplakin II (UPII), and uroplakin III (UPIII). Vesicoureteral reflux (VUR) is the most common congenital urinary tract anomaly. This disease can pose a major threat to the kidneys as twenty percent of patients with endstage renal disease are reported to have VUR. Although genetic studies for uroplakins (UPs) using mouse have been reported recently, no study has focused on UP genes expression in VUR patients. We describe here the up-regulation of UPs mRNA in exfoliated urinary cells from primary VUR patients. Methods: A real-time RT-PCR for UPs mRNA was performed on exfoliated urothelial cells from primary VUR and control samples. UPs mRNA copies were calculated for each sample. The statistical differences were assessed by the Mann-Whitney U test. Receiver operator characteristic curves were constructed for analysis of the diagnostic values. Results: In the tissues, UPs gene expressions were significantly up-regulated in VUR samples relative to controls. Considering our results, all of the UP gene expressions were up-regulated in the VUR tissues. Moreover, UPs mRNA was found to be up-regulated to a greater extent in VUR than in control exfoliated urinary cells. In evaluating the measurement of urinary UPs mRNA as a screening test for VUR, the sensitivity and the specificity could be determined by the best diagnostic cutoff point. Discussion: Regarding UPs mRNA in VUR, two studies of UPII and UPIII gene knockout mouse models were reported. All of the unaffected UP transcripts were shown by Northern blotting to be up-regulated. Though these studies were in mice, the findings are compatible with our results in humans. Our studies may have less impact because the control subjects were not age-matched. However, we submit that UPs and our results can lead to clarifying the etiology of VUR in the future. Further studies are needed of samples obtained from age-adjusted pediatric patients with other urological conditions, such as cystitis, pyelonephritis, and congenital hydronephrosis. We also investigated by a (99m) technetium dimercaptosuccinic acid renal scan the relationship between UP mRNA expression and the degree of renal scarring in VUR tissue samples. Although not significant, higher expression levels were found for UP mRNAs with the increasing degree of renal scarring. These results show the feasibility of quantitative measurements for urinary UP mRNAs and the potential use in screening for VUR. In addition, our preliminary studies of RT-PCR for tissue UP mRNAs can be useful in elucidating the underlying mechanisms leading to VUR in the future. Conclusions: We submit that the quantitative measurement of urinary Ups mRNA has a potential of developing into the first non-invasive screening test for VUR.