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Role of acetylcholine in renal fibrosis

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


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.