Bladder Function in Nocturia and IC/BPS
Major focus: Circadian rhythms, Molecular pathways of Oxidative stress and their implications in Nocturia and IC/BPS
Circadian dysregulation and nocturia
Nocturia, a condition with frequent urination due to bladder dysfunction during the sleeping phase, impacts 50 million people and carries a financial burden estimated to be 62.5 billion dollars per year in the United States. One in three adults older than 30 years of age, makes at least two trips to the bathroom every night, and the severity of nocturia worsens with age. Our working hypothesis is that peripheral circadian dysregulation of the bladder is a basis for nocturia. The sensation of bladder fullness has a circadian rhythm, which is created by functional circadian changes of PIEZO1 and TRPV4, controlled by CLOCK gene to be active during wakefulness and inactive during sleep, wherein abnormalities of peripheral clock genes disrupt bladder fullness quiescence and induce nocturia. Also, Stress can alter circadian gene expression of the bladder during the light/dark phases and may cause nocturia via changes in circadian bladder function through dysregulation of CLOCK gene. We are trying to understand and establish the effects of circadian dysregulation on bladder dysfunction with a major focus on circadian genes like CLOCK, PER1,2 and the ion and water channels regulated by them such as PEIZO1, AQP etc.
Role of oxidative stress/ROS in IC/BPS
The pathogenesis leading to the onset of IC/BPS and relapsing flares associated with this condition are unclear. Oxidative damage and free radicals may be implicated in the development of IC/BPS as pathways shown to be involved in the IC/BPS, including JNK and ion channels like TRPs are regulated by ROS. ROS act as cell signaling molecules in normal biologic processes, and are thus present during metabolic, and physiologic processes. Oxidative stress occurs when there is an imbalance between oxidants and antioxidants, which can contribute to IC/BPS. Our main focus is to understand the role of ROS in the development of IC/BPS by analyzing the respective molecular pathways and ion channels, with emphasis on JNKs and TRPs.