Participation of PI3K gamma in experimental cystitis induced by cyclophosphamide in mice

• Grant number: 11/09332-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2011
• End date: July 31, 2013
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Edson Antunes
• Grantee: Anderson Luiz Ferreira
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Interstitial cystitis (IC) is a chronic pathology with undetermined etiology that implicates a clinical aspect of pelvic or perineal pain, urination urgency and increase in the frequency of urination. Despite its benign character, IC causes an acute and serious psycho-social disturbance. Various mechanisms have been described in order to explain its etiology, such as: urothelial damage, mast cell activation, hyperexcitation of the afferent nerve of the bladder, inflammation and auto immune mechanisms. Due to the lack of certainties around the disease, the treatments currently available still have low efficacy. In this context, a deeper comprehension of the mechanisms involved in the development of IC is fundamental to the pursuit of new therapeutic approaches. Inflammatory processes are controlled by various types of membrane cell receptors, such as the cytokine and chemokine receptors and growth factors with many common intracellular signaling pathways. Among these shared events, the phosphatidylinositol 3-kinase (PI3K) has been described as the agonist of many types of extracellular receptors. The fact the (PI3K) pathway plays a pivotal role in different cell responses and the fact that it is impaired during the development of different diseases, such as cancer, chronic inflammation makes this signaling pathway an important therapeutic target. This work aims at the evaluation the participation of PI3-g in experimental cyclosphosphamide-induced cystitis. For that purpose, the functionality of the urinary bladder and the participation of inflammatory mediators will be evaluated in PI3K signaling-deficient animals. (AU)