Pannexin 1 Channel, a Novel Molecular Mediator and Potential Therapeutic Target for Interstitial Cystitis
Abstract
This project focuses on Interstitial Cystitis (IC) and mechanisms whereby stress and urothelial dysfunction lead to development of IC symptoms. The study premise 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 new data obtained from studies with Panx1-null mice demonstrated that Panx1 absence reduced the stress-induced IC-like urinary symptoms observed in the animal model and precluded the symptoms persistence, which in wildtype mice is observed long after stress cessation. New data from invitro studies demonstrated that exposure to urine-like K+ levels induced significant urothelial ATP release that was greatly amplified when combined with mechanical stimulation (mimicking bladder distension) and was inhibited by pharmacologicalPanx1 blockade. These findings are in line with our overarching hypothesis of the key roles played by Panx1 channels and exposure to urinary K+ in triggering the IC symptoms in the context of stress-induced disruption of the urothelial barrier.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2023
- Accession Number
- AD1212438
Entities
People
- Sylvia O. Suadicani
Organizations
- Albert Einstein College of Medicine