Cell signalling in urothelium

A problem presented at the UK MMSG Nottingham 2002.

Presented by:
Prof Jenny Southgate (Department of Biology, University of York)
Participants:
A Hazel, O Jensen, A Jones, J Keener, J Southgate, P Woodroffe

Problem Description

The urothelium is a stratified layer of epithelial cells that lines the interior of the bladder. Under normal conditions it undergoes large changes in surface area while maintaining a tight barrier to the diffusion of urea and other potentially toxic constituents of urine. Although under normal conditions urothelial cells are quiescent, when damaged they have a remarkable capacity to repair themselves rapidly. This process is controlled by a delicate balance between cell differentiation and proliferation. In vitro experimentation has revealed coupling between intracellular signalling pathways regulating these two processes. The Study Group is asked to develop mathematical models of these pathways.

Study Group Report

The model developed matches the experimental observations of a very small response after one hour of drug application and a much greater response after two hours of drug application. We have shown that the first model of a simple drug activation pathway was not sufficient to achieve this effect and that the presence of a feedback loop is required. We have argued the case and demonstrated the possibility of FATP causing such a loop. It remains to be seen whether this loop or perhaps another actually operates in urothelium.

Many of the parameters used in the model had to be estimated from knowledge of rates of similar reactions, often in non-urothelial cells. Hence, the model is more qualitative than quantitative, and hopefully more laboratory work can be done to gain accurate parameter and rate values to allow us to model the system thoroughly.

Download the full report

Follow-Up Activities

The following publications have been written as a result of this problem:

Modelling cell signalling and differentiation in the urothelium
PJ Woodroffe, JR King, CL Varley & J Southgate (2005)
Bulletin of Mathematical Biology 67, 369–389.