Perfil de expressão de genes envolvidos nas vias conônica e não-canônica da WNT no tecido cerebral de pacientes portadores de displasia cortical focal
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da PUC_RS |
Texto Completo: | https://tede2.pucrs.br/tede2/handle/tede/10486 |
Resumo: | Focal cortical dysplasias (focal cortical dysplasia, FCD) are a type of malformation of cerebral cortical development. FCD is considered one of the most prevalent forms of refractory epilepsy and the main cause of this pathology in children. Cortical delamination and swollen cells are the main histopathological findings found in the affected tissue. FCD is classified into at least three types with different subtypes, and its differentiation is determined by means of magnetic resonance imaging, where it is possible to observe the areas affected by FCD, allowing, when possible or necessary, surgery to remove the FCD. dysplastic region. The lack of animal and cellular models makes research difficult to understand the pathogenesis of FCD. It is a consensus that the disease has a genetic character, however all the mechanisms involved are not yet fully known. It is known that the expression of proteins such as Wnt and β-catenin may be of great importance for the pathogenesis of DGFs. The alteration in the expression of these proteins has important consequences on cell migration and differentiation, which are definitive processes for the alterations found in dysplasia. The silencing or activation of genes related to FCDs is vital for the establishment of these malformations. The present study evaluated the expression of 84 genes related to the activity of the Wnt/β-catenin pathway, through real-time PCR, comparing patients with FCD to the control group. Several genes of the Wnt pathway were found with increased expression. The expression of β-catenin remained the same as the control, however, some of its transcripts showed increased expression. Wnt genes were increased, along with frizzled receptors and the LRP5 co-receptor. The LRP6 co-receptor remained with the same expression as the control. |
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Machado, Denise Cantarellihttp://lattes.cnpq.br/3647042041612695Marinowic, Daniel Rodrigohttp://lattes.cnpq.br/5357079517399761http://lattes.cnpq.br/3855955183346007Xavier, Fernando Antonio Costa2022-09-26T13:59:06Z2022-01-28https://tede2.pucrs.br/tede2/handle/tede/10486Focal cortical dysplasias (focal cortical dysplasia, FCD) are a type of malformation of cerebral cortical development. FCD is considered one of the most prevalent forms of refractory epilepsy and the main cause of this pathology in children. Cortical delamination and swollen cells are the main histopathological findings found in the affected tissue. FCD is classified into at least three types with different subtypes, and its differentiation is determined by means of magnetic resonance imaging, where it is possible to observe the areas affected by FCD, allowing, when possible or necessary, surgery to remove the FCD. dysplastic region. The lack of animal and cellular models makes research difficult to understand the pathogenesis of FCD. It is a consensus that the disease has a genetic character, however all the mechanisms involved are not yet fully known. It is known that the expression of proteins such as Wnt and β-catenin may be of great importance for the pathogenesis of DGFs. The alteration in the expression of these proteins has important consequences on cell migration and differentiation, which are definitive processes for the alterations found in dysplasia. The silencing or activation of genes related to FCDs is vital for the establishment of these malformations. The present study evaluated the expression of 84 genes related to the activity of the Wnt/β-catenin pathway, through real-time PCR, comparing patients with FCD to the control group. Several genes of the Wnt pathway were found with increased expression. The expression of β-catenin remained the same as the control, however, some of its transcripts showed increased expression. Wnt genes were increased, along with frizzled receptors and the LRP5 co-receptor. The LRP6 co-receptor remained with the same expression as the control.As displasias corticais focais (focal cortical dysplasia, FCD) são um tipo de malformação do desenvolvimento cortical cerebral. A FCD é considerada uma das formas mais predominantes de epilepsia refratária e a principal causa desta patologia em crianças. Delaminação cortical e células abalonadas são os principais achados histopatológicos encontrados no tecido afetado. A FCD é classificada em, ao menos, três tipos com diversos subtipos, sendo sua diferenciação determinada por meio do exame de imagem por ressonância magnética, onde é possível observar as áreas afetadas pela FCD possibilitando, quando possível ou necessário, a cirurgia de remoção da região displásica. A falta de modelos animais e celulares dificulta a pesquisa para a compreensão da patogenia da FCD. É consenso que a doença apresenta um caráter genético, no entanto ainda não se conhece completamente todos os mecanismos envolvidos. Sabe-se que a expressão de proteínas como Wnt e β-catenina pode ser de grande importância para a patogenia das FCDs. A alteração da expressão destas proteínas tem importantes consequências na migração e diferenciação celular, os quais são processos definitivos para as alterações encontradas na displasia. O silenciamento ou ativação de genes relacionados às FCDs é vital para o estabelecimento destas malformações. O presente estudo avaliou expressão de 84 genes relacionados à atividade da via Wnt/β-catenina, por meio da PCR em tempo real, comparando pacientes com FCD ao grupo controle. Diversos genes da via Wnt encontravam-se com expressão aumentada. A expressão de β-catenina permaneceu igual ao controle, no entanto, alguns de seus transcritos apresentavam aumento de expressão. Os genes da Wnt estavam aumentados, junto com os receptores frizzled e o co-receptor LRP5. O co-receptor LRP6 permaneceu com expressão igual à do controle.Submitted by PPG Medicina e Ciências da Saúde (medicina-pg@pucrs.br) on 2022-09-14T12:31:49Z No. of bitstreams: 1 Tese Final 05-07-22-Revisada.pdf: 2038527 bytes, checksum: 653821e98aa8e8861745ac37f351c0ec (MD5)Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2022-09-26T13:50:46Z (GMT) No. of bitstreams: 1 Tese Final 05-07-22-Revisada.pdf: 2038527 bytes, checksum: 653821e98aa8e8861745ac37f351c0ec (MD5)Made available in DSpace on 2022-09-26T13:59:06Z (GMT). No. of bitstreams: 1 Tese Final 05-07-22-Revisada.pdf: 2038527 bytes, checksum: 653821e98aa8e8861745ac37f351c0ec (MD5) Previous issue date: 2022-01-28Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfhttps://tede2.pucrs.br/tede2/retrieve/185561/TES_FERNANDO_ANTONIO_COSTA_XAVIER_CONFIDENCIAL.pdf.jpgporPontifícia Universidade Católica do Rio Grande do SulPrograma de Pós-Graduação em Medicina e Ciências da SaúdePUCRSBrasilEscola de MedicinaDisplasia Cortical FocalqPCRWntBeta-CateninaEpilepsiaFocal Cortical DysplasiaqPCRWntBeta-CateninEpilepsyCIENCIAS DA SAUDE::MEDICINAPerfil de expressão de genes envolvidos nas vias conônica e não-canônica da WNT no tecido cerebral de pacientes portadores de displasia cortical focalinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisTrabalho será publicado como artigo ou livro60 meses26/09/2027-721401722658532398500500500600-224747486637135387-9693694523087866273590462550136975366info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSTHUMBNAILTES_FERNANDO_ANTONIO_COSTA_XAVIER_CONFIDENCIAL.pdf.jpgTES_FERNANDO_ANTONIO_COSTA_XAVIER_CONFIDENCIAL.pdf.jpgimage/jpeg4129https://tede2.pucrs.br/tede2/bitstream/tede/10486/4/TES_FERNANDO_ANTONIO_COSTA_XAVIER_CONFIDENCIAL.pdf.jpg536b27dfae9675bdde2fd56652cbd927MD54TEXTTES_FERNANDO_ANTONIO_COSTA_XAVIER_CONFIDENCIAL.pdf.txtTES_FERNANDO_ANTONIO_COSTA_XAVIER_CONFIDENCIAL.pdf.txttext/plain2405https://tede2.pucrs.br/tede2/bitstream/tede/10486/3/TES_FERNANDO_ANTONIO_COSTA_XAVIER_CONFIDENCIAL.pdf.txt333eb5914f7ef710f0eb21620a665e53MD53ORIGINALTES_FERNANDO_ANTONIO_COSTA_XAVIER_CONFIDENCIAL.pdfTES_FERNANDO_ANTONIO_COSTA_XAVIER_CONFIDENCIAL.pdfapplication/pdf421543https://tede2.pucrs.br/tede2/bitstream/tede/10486/2/TES_FERNANDO_ANTONIO_COSTA_XAVIER_CONFIDENCIAL.pdf6bae7911866e4f88296cb32fdfa4a2f2MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-8590https://tede2.pucrs.br/tede2/bitstream/tede/10486/1/license.txt220e11f2d3ba5354f917c7035aadef24MD51tede/104862022-09-26 12:00:26.592oai:tede2.pucrs.br:tede/10486QXV0b3JpemE/P28gcGFyYSBQdWJsaWNhPz9vIEVsZXRyP25pY2E6IENvbSBiYXNlIG5vIGRpc3Bvc3RvIG5hIExlaSBGZWRlcmFsIG4/OS42MTAsIGRlIDE5IGRlIGZldmVyZWlybyBkZSAxOTk4LCBvIGF1dG9yIEFVVE9SSVpBIGEgcHVibGljYT8/byBlbGV0cj9uaWNhIGRhIHByZXNlbnRlIG9icmEgbm8gYWNlcnZvIGRhIEJpYmxpb3RlY2EgRGlnaXRhbCBkYSBQb250aWY/Y2lhIFVuaXZlcnNpZGFkZSBDYXQ/bGljYSBkbyBSaW8gR3JhbmRlIGRvIFN1bCwgc2VkaWFkYSBhIEF2LiBJcGlyYW5nYSA2NjgxLCBQb3J0byBBbGVncmUsIFJpbyBHcmFuZGUgZG8gU3VsLCBjb20gcmVnaXN0cm8gZGUgQ05QSiA4ODYzMDQxMzAwMDItODEgYmVtIGNvbW8gZW0gb3V0cmFzIGJpYmxpb3RlY2FzIGRpZ2l0YWlzLCBuYWNpb25haXMgZSBpbnRlcm5hY2lvbmFpcywgY29ucz9yY2lvcyBlIHJlZGVzID9zIHF1YWlzIGEgYmlibGlvdGVjYSBkYSBQVUNSUyBwb3NzYSBhIHZpciBwYXJ0aWNpcGFyLCBzZW0gP251cyBhbHVzaXZvIGFvcyBkaXJlaXRvcyBhdXRvcmFpcywgYSB0P3R1bG8gZGUgZGl2dWxnYT8/byBkYSBwcm9kdT8/byBjaWVudD9maWNhLgo=Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.pucrs.br/tede2/PRIhttps://tede2.pucrs.br/oai/requestbiblioteca.central@pucrs.br||opendoar:2022-09-26T15:00:26Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false |
dc.title.por.fl_str_mv |
Perfil de expressão de genes envolvidos nas vias conônica e não-canônica da WNT no tecido cerebral de pacientes portadores de displasia cortical focal |
title |
Perfil de expressão de genes envolvidos nas vias conônica e não-canônica da WNT no tecido cerebral de pacientes portadores de displasia cortical focal |
spellingShingle |
Perfil de expressão de genes envolvidos nas vias conônica e não-canônica da WNT no tecido cerebral de pacientes portadores de displasia cortical focal Xavier, Fernando Antonio Costa Displasia Cortical Focal qPCR Wnt Beta-Catenina Epilepsia Focal Cortical Dysplasia qPCR Wnt Beta-Catenin Epilepsy CIENCIAS DA SAUDE::MEDICINA |
title_short |
Perfil de expressão de genes envolvidos nas vias conônica e não-canônica da WNT no tecido cerebral de pacientes portadores de displasia cortical focal |
title_full |
Perfil de expressão de genes envolvidos nas vias conônica e não-canônica da WNT no tecido cerebral de pacientes portadores de displasia cortical focal |
title_fullStr |
Perfil de expressão de genes envolvidos nas vias conônica e não-canônica da WNT no tecido cerebral de pacientes portadores de displasia cortical focal |
title_full_unstemmed |
Perfil de expressão de genes envolvidos nas vias conônica e não-canônica da WNT no tecido cerebral de pacientes portadores de displasia cortical focal |
title_sort |
Perfil de expressão de genes envolvidos nas vias conônica e não-canônica da WNT no tecido cerebral de pacientes portadores de displasia cortical focal |
author |
Xavier, Fernando Antonio Costa |
author_facet |
Xavier, Fernando Antonio Costa |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Machado, Denise Cantarelli |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/3647042041612695 |
dc.contributor.advisor-co1.fl_str_mv |
Marinowic, Daniel Rodrigo |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/5357079517399761 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3855955183346007 |
dc.contributor.author.fl_str_mv |
Xavier, Fernando Antonio Costa |
contributor_str_mv |
Machado, Denise Cantarelli Marinowic, Daniel Rodrigo |
dc.subject.por.fl_str_mv |
Displasia Cortical Focal qPCR Wnt Beta-Catenina Epilepsia |
topic |
Displasia Cortical Focal qPCR Wnt Beta-Catenina Epilepsia Focal Cortical Dysplasia qPCR Wnt Beta-Catenin Epilepsy CIENCIAS DA SAUDE::MEDICINA |
dc.subject.eng.fl_str_mv |
Focal Cortical Dysplasia qPCR Wnt Beta-Catenin Epilepsy |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::MEDICINA |
description |
Focal cortical dysplasias (focal cortical dysplasia, FCD) are a type of malformation of cerebral cortical development. FCD is considered one of the most prevalent forms of refractory epilepsy and the main cause of this pathology in children. Cortical delamination and swollen cells are the main histopathological findings found in the affected tissue. FCD is classified into at least three types with different subtypes, and its differentiation is determined by means of magnetic resonance imaging, where it is possible to observe the areas affected by FCD, allowing, when possible or necessary, surgery to remove the FCD. dysplastic region. The lack of animal and cellular models makes research difficult to understand the pathogenesis of FCD. It is a consensus that the disease has a genetic character, however all the mechanisms involved are not yet fully known. It is known that the expression of proteins such as Wnt and β-catenin may be of great importance for the pathogenesis of DGFs. The alteration in the expression of these proteins has important consequences on cell migration and differentiation, which are definitive processes for the alterations found in dysplasia. The silencing or activation of genes related to FCDs is vital for the establishment of these malformations. The present study evaluated the expression of 84 genes related to the activity of the Wnt/β-catenin pathway, through real-time PCR, comparing patients with FCD to the control group. Several genes of the Wnt pathway were found with increased expression. The expression of β-catenin remained the same as the control, however, some of its transcripts showed increased expression. Wnt genes were increased, along with frizzled receptors and the LRP5 co-receptor. The LRP6 co-receptor remained with the same expression as the control. |
publishDate |
2022 |
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2022-09-26T13:59:06Z |
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2022-01-28 |
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Pontifícia Universidade Católica do Rio Grande do Sul |
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