System level changes in gene expression in maturing XXXX .

@entity24832 @entity25734 @entity322 @entity1494 @entity21028 @entity19 @entity43441 @entity5780 @entity31883 @entity641 @entity52724 @entity600 @entity177 @entity17652 @entity74 @entity2182 @entity24896
PURPOSE: Bladder problems clinically present early in life as @entity600 that often lead to @entity177 and late in life as @entity2182 , @entity322 and @entity74 . We investigated the transcriptome of @entity19 @entity1494 at juvenile and adult stages by microarray to identify the pathways associated with normal, healthy growth and maturation. We hypothesized that understanding these pathways could be key to achieving bladder regeneration or reawakening normal function in the elderly population. MATERIALS AND METHODS: RNA was isolated from the mucosa at 3, 6, 20 and 30 weeks postnatally. Affymetrix   @entity19 430 v2 arrays were used to profile the expression of approximately 45,000 genes. The software program Statistical Analysis of Microarrays was used to identify genes that significantly changed during the time course. RESULTS: No genes were significantly up-regulated during maturation. However, 66 well annotated genes demonstrated a statistically significant downward trend, of which 10 of 10 were confirmed by quantitative polymerase chain reaction. The main functions affected by age were transcription, regulation of cellular processes, neurogenesis, blood vessel development and cell differentiation. Notable genes included collagens, @entity5780 , @entity17652 and several transcription factors, including @entity24896 , @entity24832 , @entity52724 , @entity25734 , @entity21028 , @entity43441 and @entity31883 . These molecules were indirectly regulated by inferred @entity641 and Egf growth factors. Analysis of gene promoter regions for overrepresented upstream transcription factor binding sites identified specificity protein 1 and epidermal growth factor receptor-specific transcription factor as potentially major transcriptional regulators driving maturation related changes. CONCLUSIONS: These findings identify a coherent set of genes that appear to be down-regulated during urothelial maturation. These genes may represent an attractive target for bladder regeneration or for treating age related loss of function.
