Understanding neuro-urothelial communication
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The urothelium lining the bladder has two major functions: (i) a barrier, to protect the bladder tissues and their nerve supply from substances within urine, and (ii) as sensory transducer that responds to chemical and mechanical stimulation by releasing substances to activate sensory axons in the bladder wall. Whereas the barrier function is well accepted, the transducer properties have been inferred by strong, but indirect evidence. We have developed a neuro-urothelial co-culture system so can now directly study intercellular communication between urothelial cells and sensory neurons. We are now extending this system to incorporate autonomic ganglion neurons. This is relevant to understanding how the urothelium signals to nearby sensory nerve terminals and, conversely, how nerves may regulate epithelial growth and repair (relevant to conditions such as cystitis when the urothelium is damaged and, conversely, bladder cancer, when growth is dysregulated. Approaches to probe signalling between the urothelium and neurons include compartmentalised cultures in microfluidic chambers, immunofluorescence and live-cell imaging. We are also examining growth-promoting signals from the neurons that can impact on urothelial cell proliferation in vitroand their ability to drive repair in vivo.
Figure 1: Urothelial cells cultured with sensory neurons show many sites of close apposition and likely communication. Urothelial cells release as yet undefined trophic factors to promote neuronal growth.
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