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

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

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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. Web of Science Citations: 6.
MARTIN DESROSIERS; FABIANA CARDOSO PEREIRA VALERA. Brave New (Microbial) World: implications for nasal and sinus disorders. Brazilian Journal of Otorhinolaryngology, v. 85, n. 6, p. 675-677, Dez. 2019.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.