Avaliação da expressão gênica de agonistas e antagonistas da via Wnt em células ex-vivo de fibroblastos do tipo sinoviócitos humanos

• Ano de defesa: 2020
• Autor(a) principal: Tamiris de Paula Silva
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; MEDICINA - FACULDADE DE MEDICINA; Programa de Pós-Graduação em Ciências Aplicadas à Saúde do Adulto; UFMG
• Palavras-chave em Português: Proteínas Wnt; Doenças reumáticas; Doenças ósseas; Expressão gênica; Dissertação Acadêmica
• Link de acesso: http://hdl.handle.net/1843/42686; https://orcid.org/0000-0002-8570-8918

INTRODUCTION: the Wnt pathway regulates various physiological phenomena and processes throughout human life including bone development. Bone metabolism consists of stability between tissue formation and absorption. When this balance is lost, affected people may experience erosion or bone proliferation. Currently, for patients with bone absorption have several medications available while for patients with bone proliferation there are not many effective drug options. OBJECTIVES: to analyze the gene expression of the Wnt pathway agonists and antagonists in patients with rheumatoid arthritis - RA and spondyloarthritis - SpAs (ankylosing spondylitis and psoriatic arthritis). METHODOLOGY: Synovial fibroblasts were grown from seven patients, four with rheumatoid arthritis and three with spondyloarthritis (one with ankylosing spondylitis and two with psoriatic arthritis) in DMEM culture medium with fetal bovine serum. Then, from the fibroblasts, the mRNA was extracted, converted into cDNA. RT-qPCR was performed using the cDNA using the TAQMAN method. RESULTS: In all genes, there was a difference in expression between stimulated and unstimulated fibroblasts, but the statistically significant result occurred with the WNT-9A gene. With this gene, there was a reduction in expression in fibroblasts stimulated with IL-17, IL-22 and TNF-alpha in patients with rheumatoid arthritis and spondyloarthritis. Most of the results of this study were not statistically significant, proving that the hypothesis that stimuli would alter the gene expression of fibroblasts has become null. CONCLUSIONS: Some factors may have contributed to these results, such as low N sample, stimulus with cytokines, non-complete stimulus in in vitro conditions because interactions between genes and between antagonists and agonists were disregarded. Thus, further studies are necessary to confirm or not that the stimuli with cytokines do not really affect the expression of the antagonist and agonist genes that make up the WNT pathway. KEY WORDS: Wnt proteins, rheumatic diseases, bone diseases, gene expression.