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Subproject 4

Molecular strategies involving the transcription factor p53 to support the functional reinnervation of dysfunctional urethral sphincters

Urinary incontinence can have age- and injury-related causes that lead to a loss of sphincter cells. It can also be caused by age- and injury-related disorders that affect the autonomous sensory and motor nerves. It is not yet known whether the reduced innervation of the sphincter is reversible, whether regenerating nerve cells and externally supplied autologous myoblasts affect each other, and whether muscle (progenitor) cells that are extracorporally prepared, expanded and injected can establish contact with existing sphincter nerves. We have been able to show that limited, spontaneous, axonal regeneration is directly related with an improvement in muscle function. This project is therefore focused on assessing novel pro-regenerative molecular strategies and their influence on the sphincter muscles and the growth behaviour of implanted cells from subproject 1 in the rat model.

We have been able to show that the p53 transcription factor, which controls the expression of pro-axonal growth molecules such as GAP43 and cGKI, is required for the physiological regeneration of the nerves. It can therefore be assumed that the gene- or drug-mediated enhancement of the p53-dependent signalling cascade supports the axonal regeneration of injured hypogastric nerves and limits sphincter dysfunction. The project focuses specifically on the regeneration of nerves, the outgrowth of nerves, the p53-dependent molecular changes and the growth behaviour of implanted cells. The project also plans to functionally visualise the reinnervation of the sphincter using periurethral electromyography.


Dr. Simone Di Giovanni

Hertie Institute for Clinical Brain Research
Head of the Laboratory for Neuroregeneration

© Department of Urology Tuebingen - supported by "Förderverein Urologie e. V." - Nonprofit association