Role of Acetylcholine in Renal Fibrosis

• Grant number: 11/19171-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2012
• End date: December 31, 2012
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Yuri Felipe de Souza Pereira Guise
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Acetylcholine (Ach) is a known neurotransmitter involved with many physiological process. Recent studies revealed that acetycholine also play a central role in anti-inflammatory responses, mainly through the neuronal nicotinic acetylcholine receptors ±7 (±7 nAChR) present in macrophages. That pathway was denominated the colinergic anti-inlammatory pathway. The activation of these receptors lead to a smaller synthesis of pro-inflammatory citocines, such as interleucin (IL-1², IL-6, IL-8) and tumoral necrosis factor alpha (TNF±), through a nuclear factor kappa B (NF-ºB) dependant via that block high mobility group box 1 (HMGB-1) from leaving the celular nucleus and act as a pro-inflammatory substance. This project seek to evaluate the inflammatory and fibrotic pattern in mice that are Knockdown (KD) to Vesicular Acetylcholine transporter (VAChT)in an Unilateral Ureter Obstruction (UUO)by analysis of immunologic mediators, histology and cell infiltration.The KD mice will be treated with PNU-282987, a full ±7 nAChR agonist,to revert the pro-fibrotic and pro-inflammatory pattern.