Kids Kidney Research

Congenital (i.e. present at birth) bladder abnormalities are often associated with kidney failure and have major clinical implications for affected individuals and considerable social implications for their families.  To understand how these devastating diseases arise, it is necessary to understand how the normal bladder grows: at present, unfortunately, little is known about specific molecules which might orchestrate and directly drive normal bladder development.  Recent studies from this laboratory showed, for the first time, that a molecule called vascular endothelial growth factor was a remarkable growth stimulus to the fetal bladder.  In the current study the manner in which this molecule stimulates bladder growth will be explored, which will also begin to define whether it might also be implicated in congenital bladder disease.  This study is seen as a prelude to a programme of work to tissue-engineer bladders for transplantation therapies for patients with malformed bladders.

 

Acheivements:

 

The work outlined in this grant was performed in the Nephro-Urology Unit (by Adrian Woolf and David Long – David’s salary is provided by the grant).

 

Bladders were collected from embryonic day E13 and E18 and a microarray performed to look for differences in gene expression. This has provided novel insights into the molecules that regulate the development of the mouse bladder and several potential lines of further investigation. The work arising from this study will be presented at the European Society of Pediatric Urology meeting and a manuscript is currently in preparation.

 

We used tissues from ovine models of fetal bladder outflow obstruction to determine expression patterns of the VEGF-A signalling axis, versus time-matched normal samples. We demonstrated altered expression of VEGF following bladder outflow obstruction and this work will be presented at the European Society of Pediatric Urology meeting

 

Experiments have been performed to stimulate isolated bladders with VEGF and also midkine (a growth factor found to be altered in our microarray). Analysis of these experiments is currently being performed.

 

Additionally, David Long and Adrian Woolf have published studies looking at the potential gene therapy using a related growth factor Angiopoietin-1 in folic-acid induced acute renal disease. This work was previously funded by the Kids Kidney Research and will be published in Kidney International by the end of May 2008. In addition, Dr. Long and Professor Woolf have submitted an invited review to the Journal of American Society of Nephrology on the roles of angiopoietins in kidney development and disease.

 

In April 2008, Dr. David Long was awarded a Senior non-clinical fellowship from Kidney Research UK for four years entitled “Roles of angiopoietins in epithelial-endothelial interactions: using the renal glomerulus as a model system” to continue his research.