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Doctoral Thesis
DOI
https://doi.org/10.11606/T.17.2020.tde-05102020-132853
Document
Author
Full name
Mariana Lima Coêlho Silveira
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2020
Supervisor
Committee
Valera, Fabiana Cardoso Pereira (President)
Arruda, Luisa Karla de Paula
Kosugi, Eduardo Macoto
Tamashiro, Edwin
Title in Portuguese
Pesquisa de miRNA em pacientes com rinossinusite crônica com pólipo nasal
Keywords in Portuguese
MicroRNA
Pólipo nasal
Rinossinusite crônica
Abstract in Portuguese
Estudos indicam a importância de microRNAs (miRNA) em pacientes portadores de doenças inflamatórias crônicas, dentre elas a rinossinusite crônica com pólipo nasal (RSCcPN). No entanto, estudos que tenham avaliado a sua expressão nos pólipos nasais e a repercussão clínica decorrente são escassos em literatura. Foram objetivos do estudo: comparar a presença de miRNAs em pacientes com RSCcPN aos controles; associar a expressão de miRNA aos diversos padrões inflamatórios (Th1, Th2, Th17 e Treg) e avaliar a sua influência em aspectos clínicos como extensão da doença e a presença de sinais e sintomas. Amostras de pólipo nasal de pacientes com RSCcPN (sem vigência de tratamento clínico) e mucosa nasal de concha média dos controles foram colhidas para processamento. Os níveis de 1996 miRNA maduros humanos foram comparados por meio de microarray, e os miRNA diferentemente expressos tiveram seus níveis confirmados por qRT-PCR. As dosagens de citocinas pró-inflamatórias foram medidas por Luminex. A comparação entres os dois grupos se deu por meio de testes não-pareados. Após, os miRNAs diferentemente expressos pelos dois exames foram correlacionados com as concentrações das citocinas pró-inflamatórias e com os dados clínicos, aplicando-se testes de correlação paramétricos. Após as duas análises (microarray e qRT-PCR), seis miRNAs: hsa-miR-205-5p, hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-378a-3p, hsa-miR-449a e hsa-miR-449b-5p tiveram expressão significativamente diferente, todos com níveis aumentados nos pólipos nasais em comparação aos controles. Houve correlação direta positiva e significativa entre miR-205-5p com a expressão de IL-5, o grau de eosinofilia e a piora do padrão clínico (SNOT-22). O miRNA 205- 5p parece ser muito importante na fisiopatogênese da RSCcPN, aumentando o processo inflamatório, sobretudo para citocinas Th2, havendo relação significativa com a expressão de IL-5, o grau de eosinofilia e com a piora no escore de qualidade de vida.
Title in English
MicroRNA expression profile of nasal polyposis
Keywords in English
Chronic rhinosinusitis
MicroRNA
Nasal polyps
Abstract in English
Studies have highlighted the importance of microRNAs (miRNA) in patients with chronic inflammatory diseases, among them Chronic rhinosinusitis with nasal polyps (CRSwNP). However, few studies evaluated the expression of miRNA on nasal polyps, and the clinical impact related to them. The objectives of this study were: 1) to compare the presence of miRNA in patients with CRSwNP to controls; 2) to associate their expression to inflammatory patterns (Th1, Th2, Th17 and Treg); and 3) to evaluate the influence on clinical outcomes, such as extensiveness of the disease and intensity of symptoms. Samples of nasal polyp were collected from patients with CRSwNP (with a wash out period of one month), while middle turbinate mucosa were obtained from controls. The levels of 1996 mature human miRNAs were analyzed by microarray, and those differently expressed between groups were confirmed by qRT-PCR. Pro-inflammatory cytokines were measured by Luminex. The comparison between groups was performed with unpaired statistical analyses. miRNAs that were differently expressed were correlated to the concentration of pro- inflammatory cytokines and with clinical data, through parametric correlation tests. After both assays (microarray and qRT-PCR), six miRNAs were up-regulated on nasal polyps: miR-205-5p, miR-221-3p, miR-222-3p, miR-378a-3p, miR-449a and miR-449b-5p. There was a significantly positive correlation between miR-205-5p, and: IL-5 concentration; tissue eosinophilia; and worst SNOT-22. miRNA 205-5p seems to be a very important miRNA in CRSwNP physiopathology, inducing the inflammatory process (especially of Th2 cytokines, with a positive relationship with IL-5 concentration); increasing the eosinophil level on nasal tissue and worsening quality of life scores.
 
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Publishing Date
2020-10-26
 
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