Normalization of Epidermal Growth Factor (EGF) Mediated Alterations in Interstitial Cystitis (IC) Bladder Urothelial Cells (BUC) Correlate with Normalization of Adenosine Triphosphate (ATP) Alterations

Todd Lehrfeld*, Yan Sun*, Toby C Chai
University of Maryland, Baltimore, MD

Introduction:
Cultured IC BUC, compared to control BUC, secrete more EGF and release more ATP when stimulated with exogenous ATP. We determined if addition of exogenous EGF to normal BUC induced higher ATP release (e.g. convert from normal to IC phenotype) and whether genistein, which blocks EGF-mediated phosphorylation, reduced ATP levels (e.g. convert from IC to normal phenotype).
Methods:
Cultured IC cells were treated with genistein (100uM) while normal cells were exposed to EGF. After this, 30 uM exogenous ATP were added to the cells and supernatants collected at various times for ATP measurements.
Results:
Genistein treatment significantly reduced ATP release by IC cells (Figure 1) whereas EGF treatment significantly increased ATP release by normal cells in response to the exogenous ATP (Figure 2, only ATP at time 0 represented). Asterisks represent p<0.05.
Conclusions:
The phenotypes of IC and normal cells (in terms of response to exogenous ATP) could be switched by treatment with genistein and EGF, respectively. This suggests that there is a link between the EGF-cytokine and purinergic pathway in the human BUC. Further understanding of these pathways will not only increase our understanding of urothelial cellular physiology, but could lead to novel treatments for IC.

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