In vitro model to uncover new pathways of lung alveolar epithelial repair

Detalhes bibliográficos
Autor(a) principal: Silva, Manuel António Freire Dias da
Data de Publicação: 2022
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/54266
Resumo: Tese de Mestrado, Biologia Evolutiva e do Desenvolvimento, 2022, Universidade de Lisboa, Faculdade de Ciências
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spelling In vitro model to uncover new pathways of lung alveolar epithelial repairlesão pulmonar agudacélulas alveolaresimunologia da mucosaCCR10CCL28Teses de mestrado - 2022Departamento de Biologia AnimalTese de Mestrado, Biologia Evolutiva e do Desenvolvimento, 2022, Universidade de Lisboa, Faculdade de CiênciasAcute Respiratory Distress Syndrome (ARDS) is an inflammatory condition developed from parenchyma damage that ultimately leads to loss of aerated tissue. In the lung, the gas exchange occurs in the alveoli comprised by alveolar type (AT) 2 cells and AT1 cells. AT2 are known to be the alveolar stem cells as they can transdifferentiate into AT1 cells or dedifferentiate trough TGF-β driven epithelial-mesenchymal transition (EMT). In abnormal conditions, such as ARDS, the alveolar repair is impaired and both processes lead to a compromised parenchymal structure and gas exchange. For this reason, the mechanisms underlying the repair and differentiation should be further understood. Recent data suggest that epithelial CCR10 expression is not only associated with evolution towards fibrosis, but also with epithelial mobility. For this reason, we aimed to investigate the impact of different cytokines on CCR10 expression in alveolar epithelial cells in a wound healing assay. We used 7-day 2D cultures of the human A549 cell line, which are lung adenocarcinoma epithelial cells that resemble AT2 cells in vitro. After manual wound making, cells were exposed to IFNγ (type I), IL13 (type II), IL22 (type III), IL1β+IL6 (pro-inflammatory), TGFβ (EMT), GM-CSF and CCL28 (expressed by AT2 cells in demanding conditions). We found that CCL28, a CCR10 ligand, and IL13 increased the mean CCR10 expression by A549 cells. The levels of this chemokine receptor and frequency of KI-67+ cells were negatively correlated with percentage of wound closure, suggesting that like cell proliferation, CCR10 expression impacts wound repair. Interestingly, we observed that CCR10 highest mean expression was in cells in intermediate state, as we characterized in flow cytometry as Podoplanin+CD63+ . Using this same technique, we assessed A549 cell differentiation and observed that this process occurred in all conditions except for TGFβ and IFNγ, which were associated with an increase in Vimentin and decrease in E-cadherin levels, both characteristics of the EMT process. Despite the bigger frequency of AT2-like cells, neither TGFβ nor IFNγ had an effect on the production of pro-SFTPC, a marker of AT2 cell function, opposing CCL28 and GM-CSF that upregulated it. These results lead us to conclude that the CCL28/CCR10 axis may play a role in epithelial repair as CCL28 is a chemokine released by epithelial cells in pro-inflammatory/hypoxemic conditions as observed in ARDS. We propose that further studies should be done to assess the true function of this receptor in alveolar epithelial cells and intrinsic pathways that regulate CCR10 expression in a context of ARDS.Fernandes, Susana MendesCarlos, Ana Rita Cabral Martins, 1985-Repositório da Universidade de LisboaSilva, Manuel António Freire Dias da202220222025-04-30T00:00:00Z2022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10451/54266enginfo:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:00:41Zoai:repositorio.ul.pt:10451/54266Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:05:10.539022Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv In vitro model to uncover new pathways of lung alveolar epithelial repair
title In vitro model to uncover new pathways of lung alveolar epithelial repair
spellingShingle In vitro model to uncover new pathways of lung alveolar epithelial repair
Silva, Manuel António Freire Dias da
lesão pulmonar aguda
células alveolares
imunologia da mucosa
CCR10
CCL28
Teses de mestrado - 2022
Departamento de Biologia Animal
title_short In vitro model to uncover new pathways of lung alveolar epithelial repair
title_full In vitro model to uncover new pathways of lung alveolar epithelial repair
title_fullStr In vitro model to uncover new pathways of lung alveolar epithelial repair
title_full_unstemmed In vitro model to uncover new pathways of lung alveolar epithelial repair
title_sort In vitro model to uncover new pathways of lung alveolar epithelial repair
author Silva, Manuel António Freire Dias da
author_facet Silva, Manuel António Freire Dias da
author_role author
dc.contributor.none.fl_str_mv Fernandes, Susana Mendes
Carlos, Ana Rita Cabral Martins, 1985-
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Silva, Manuel António Freire Dias da
dc.subject.por.fl_str_mv lesão pulmonar aguda
células alveolares
imunologia da mucosa
CCR10
CCL28
Teses de mestrado - 2022
Departamento de Biologia Animal
topic lesão pulmonar aguda
células alveolares
imunologia da mucosa
CCR10
CCL28
Teses de mestrado - 2022
Departamento de Biologia Animal
description Tese de Mestrado, Biologia Evolutiva e do Desenvolvimento, 2022, Universidade de Lisboa, Faculdade de Ciências
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022-01-01T00:00:00Z
2025-04-30T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/54266
url http://hdl.handle.net/10451/54266
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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