445 GENES AND MOLECULAR PATHWAYS COMMON TO THE RODENT MODEL OF UNILATERAL URETERAL OBSTRUCTION AND HUMAN URETEROPELVIC JUNCTION OBSTRUCTION

Article Outline

• INTRODUCTION AND OBJECTIVES
• METHODS
• RESULTS
• CONCLUSIONS
• Copyright

Back to Article Outline

INTRODUCTION AND OBJECTIVES 

The molecular response of the developing kidney to unilateral ureteral obstruction (UUO) has been extensively studied in the rodent model. The recent application of proteomic tools to discover differentially expressed proteins in the urine of infants with ureteropelvic junction obstruction (UPJO) represents a promising non invasive approach to the understanding of the pathophysiologic processes of the human disease. In this analysis, we compare literature derived molecules implicated in the pathophysiology of experimental UUO to up and down regulated molecules derived from human unilateral grade 4 UPJO urinary proteomic data.

Back to Article Outline

METHODS 

The dataset for the rodent model was derived from a review of the literature since 2000. The dataset for the human disease was derived from the whole urinary proteome analysis by LC-MS/MS of 70 specimens from infants with unilateral grade 4 UPJO and 36 age matched normal controls. The datasets were uploaded to Ingenuity Pathway Analysis (IPA;www.Ingenuity.com) and compared for common genes, functions and networks.

Back to Article Outline

RESULTS 

There were 186 entries in the experimental list, 132 entries in the 1-6 months and 90 in the 7-12 months UPJO age groups respectively. Only 6 originating from the experimental group are detected in the urine of infants with UPJO. These consist of beta 2 microglobulin, cartilage associated protein, epidermal growth factor, colony stimulating factor-1, N-acetylglucosaminidase and gamma-glutamyltransferase. However, there is funtional overlap between the groups resulting from the interaction with molecules with no change in their relative abundance (see table).

Back to Article Outline

CONCLUSIONS 

The experimental model of UUO may mimic the response to obstruction-not its cause-and caution is advised in extrapolating to human UPJO. Nevertheless, the discovery of 6 shared markers of obstruction in the urine of patients has important implications. These genes can be specifically targeted for research however, pathways and functions resulting from the interaction of additional molecules (neither up or down regulated) may need to be taken into consideration as well.

• 
  • View Large Image
  • Download to PowerPoint