Interstitial cystitis (IC) is a chronic bladder disease with devastating effects on the lives of approximately 450,000 people in the United States. The etiology of IC is unknown, and there is currently no reliably effective treatment. It is therefore important to continue to search for a cause of this debilitating disorder, in order to systematically devise an effective therapy. Preliminary data indicate the presence of a low molecular weight, heat stable, factor(s) in the urine of IC patients that inhibits proliferation of cultured normal adult human bladder epithelial cells. Because a damaged bladder epithelium is a central finding in IC, it is possible that this factor(s) contributes to the pathogenesis of this disease. Substantial progress has been made in the purification and characterization of this antiproliferative factor(s). Preliminary characterization including trypsin treatment and isoelectric point determination indicates that this factor is probably an acidic peptide. Based upon this information, a sequential purification scheme has been devised that utilizes specific chromatographic methods to obtain an approximately 50-fold increase in specific activity of this peptide(s) with an active fraction that contains only two peaks by UV spectrometry. Further purification and characterization of this peptide(s) from additional IC patients is the first priority, with attempts to determine whether it is excreted into the urine or produced by cells from the upper or lower urinary tract. Whether the peptide(s) is glycosylated and the general types of sugar moieties present will also be assessed, and its antiproliferative activity confirmed by blocking experiments using monospecific polyclonal rabbit antibodies. The role of this peptide(s) in the pathogenesis of IC will be evaluated by correlating the amount of the peptide(s) with cystometric findings and/or symptom, severity in IC patients. Data from these studies should provide valuable information regarding the possible role of a specific urine peptide(s) in bladder epithelial cell proliferation and disease.
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