Oncosuppressor protein p53 and cyclin-dependent kinase inhibitor p21 regulate interstitial cystitis associated gene expression

Interstitial cystitis (IC) is a chronic syndrome that affects the urinary bladder. The etiology of this disease is unclear, and no effective therapies are available at this time. Although inflammation is suspected, no clear evidence for a role of conventional mediators of inflammation, such as cytokines and their downstream molecules, has been obtained to date. Our previous studies indicated that primary cell cultures derived from IC urothelium abnormally express molecules associated with cell adhesion. Here we describe a mechanism by which transcriptional changes in tight junction and adhesion molecules are mediated. Oncosuppressor proteins p53 and cyclin-dependent protein kinase inhibitor p21 directly associate with regulatory sites on the ZO-1 and E-cadherin genes, identifying important roles for p53 and p21 in driving non-oncogenic pathologies. These data also suggest that interference with these factors offers a potential therapeutic opportunity.