Epithelial repair and regeneration following injury is impaired in chronic rhinosinusitis: an investigation into mechanisms and potential therapies

• Grant number: 16/00772-1
• Support Opportunities: Scholarships abroad - Research
• Start date: August 01, 2016
• End date: July 31, 2017
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Fabiana Cardoso Pereira Valera
• Grantee: Fabiana Cardoso Pereira Valera
• Host Investigator: Martin Yvon Desrosiers
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Université de Montréal, Canada

Abstract

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by persistent inflammation. Current medical therapy is rarely curative, and the prolonged use of these medications is related to several significant side effects. In this project, we will evaluate if inadequate epithelial regeneration can perpetuate inflammation, and contribute to persistence of the disease process. This is a novel hypothesis for CRSwNP physiopathology, and could uncover new therapeutic targets for therapy. Objective: The present study aims to evaluate the involvement of deficient airway epithelial repair/regeneration and EMT (epithelial mesenchymal transition) development in CRSwNP. Methods: Nasal mucosae samples will be obtained from patients with CRSwNP (n=20), CRSsNP (n=20) and controls (n=10). Initially, nasal samples will be compared regarding the expression of epithelial, mesenchymal and EMT markers, as well as MMPs. Afterwards, epithelium will be cultured in 2-dimensional undifferentiated cultures of basal cells as well as fully differentiated cultures at the air-liquid interface. In both culture models, the effect of different conditions on epithelial repair and regeneration and on EMT molecules will be assessed upon different stimuli: 1) silencing of integrin signaling via ITGA6, Wnt/TRAIL and ²1-integrin; 2) the effect of exposure to bacterial exoproducts on this process; 3) the influence of K+ and CFTR channel activators; 4) the effect of EMT inhibitors; and finally 5) the influence of laminin, a component of the extracellular matrix. Comparison between these different experimental conditions will allow us to determine if these factors may influence airway epithelial repair and regeneration, and if they could favor chronic inflammatory process and epithelial remodeling observed in CRSwNP. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VALERA, FABIANA C. P.; RUFFIN, MANON; ADAM, DAMIEN; MAILLE, EMILIE; IBRAHIM, BADR; BERUBE, JULIE; ROUSSEAU, SIMON; BROCHIERO, EMMANUELLE; DESROSIERS, MARTIN Y.. Staphylococcus aureus impairs sinonasal epithelial repair: Effects in patients with chronic rhinosinusitis with nasal polyps and control subjects. Journal of Allergy and Clinical Immunology, v. 143, n. 2, p. 591+, FEB 2019. (16/00772-1)

MARTIN DESROSIERS; FABIANA CARDOSO PEREIRA VALERA. Admirável Mundo Novo (Microbiano): implicações para os distúrbios nasais e sinusais. Brazilian Journal of Otorhinolaryngology, v. 85, n. 6, p. 675-677, 2019-12-13. (16/00772-1)

RENTERIA, AXEL E.; VALERA, FABIANA C. P.; MANIAKAS, ANASTASIOS; ADAM, DAMIEN; FILALI-MOUHIM, ALI; RUFFIN, MANON; MFUNA, LEANDRA ENDAM; BROCHIERO, EMMANUELLE; DESROSIERS, MARTIN Y.. Azithromycin Mechanisms of Action in CRS Include Epithelial Barrier Restoration and Type 1 Inflammation Reduction. OTOLARYNGOLOGY-HEAD AND NECK SURGERY, v. N/A, p. 9-pg., 2023-05-01. (16/00772-1)