Pannexin 1 Channel, a Novel Molecular Mediator and Potential Therapeutic Target for Interstitial Cystitis
Abstract
This project focus on Interstitial Cystitis (IC) and mechanisms whereby stress and urothelial dysfunction lead to development of IC symptoms. The premise of the studies is that stress disrupts the urothelial barrier function, which results in chronic infiltration of urinary K+ into the bladder wall that generates an environment for abnormal Panx1 channel activation and expression that ultimately lead to IC and its symptoms by augmenting proinflammatory responses, intercellular signaling and stimulation of bladder sensory fibers. In this reporting period of the project, the findings that we obtained from studies conducted with the animal model of 96hrs of continuous illumination stress (CIS) demonstrated that stress not only triggers IC-like symptoms of urinary frequency, but that these symptoms persist long after stress cessation and are accompanied by a sustained increase in urothelial ATP signaling and by changes in expression of Panx1 and other key molecular mediators of the urothelial mechanotransduction system. These findings are in line with our overarching hypothesis that stress-induced disruption of the urothelial barrier triggers IC symptoms by amplifying ATP release and signaling through mechanisms that involve upregulation Panx1 expression and function in the bladder.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2022
- Accession Number
- AD1190387
Entities
People
- Sylvia O. Suadicani
Organizations
- Albert Einstein College of Medicine