Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/50219 |
Resumo: | © 2021 Kramer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
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Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina© 2021 Kramer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Retinal homeostasis relies on intricate coordination of cell death and survival in response to stress and damage. Signaling mechanisms that coordinate this process in the adult retina remain poorly understood. Here we identify Decapentaplegic (Dpp) signaling in Drosophila and its mammalian homologue Transforming Growth Factor-beta (TGFβ) superfamily, that includes TGFβ and Bone Morphogenetic Protein (BMP) signaling arms, as central mediators of retinal neuronal death and tissue survival following acute damage. Using a Drosophila model for UV-induced retinal damage, we show that Dpp released from immune cells promotes tissue loss after UV-induced retinal damage. Interestingly, we find a dynamic response of retinal cells to this signal: in an early phase, Dpp-mediated stimulation of Saxophone/Smox signaling promotes apoptosis, while at a later stage, stimulation of the Thickveins/Mad axis promotes tissue repair and survival. This dual role is conserved in the mammalian retina through the TGFβ/BMP signaling, as supplementation of BMP4 or inhibition of TGFβ using small molecules promotes retinal cell survival, while inhibition of BMP negatively affects cell survival after light-induced photoreceptor damage and NMDA induced inner retinal neuronal damage. Our data identify key evolutionarily conserved mechanisms by which retinal homeostasis is maintained.The research presented here is supported by NIH grants (R01 EY025779 and EY032197 to DL; AG057353 and EY018177 to HJ; P30 Vision Core grant to UCSF Dept of Ophthalmology), and the Research to Prevent Blindness (unrestricted grant to UCSF Dept of Ophthalmology).PLOSRepositório da Universidade de LisboaKramer, JoshuaNeves, JoanaKoniikusic, MiaJasper, HeinrichLamba, Deepak A.2021-11-30T13:53:24Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/50219engPLoS One. 2021 Oct 26;16(10):e025887210.1371/journal.pone.02588721932-6203info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:54:10Zoai:repositorio.ul.pt:10451/50219Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:01:37.110331Repositório 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 |
Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina |
title |
Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina |
spellingShingle |
Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina Kramer, Joshua |
title_short |
Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina |
title_full |
Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina |
title_fullStr |
Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina |
title_full_unstemmed |
Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina |
title_sort |
Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retina |
author |
Kramer, Joshua |
author_facet |
Kramer, Joshua Neves, Joana Koniikusic, Mia Jasper, Heinrich Lamba, Deepak A. |
author_role |
author |
author2 |
Neves, Joana Koniikusic, Mia Jasper, Heinrich Lamba, Deepak A. |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Kramer, Joshua Neves, Joana Koniikusic, Mia Jasper, Heinrich Lamba, Deepak A. |
description |
© 2021 Kramer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-11-30T13:53:24Z 2021 2021-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/50219 |
url |
http://hdl.handle.net/10451/50219 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
PLoS One. 2021 Oct 26;16(10):e0258872 10.1371/journal.pone.0258872 1932-6203 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
PLOS |
publisher.none.fl_str_mv |
PLOS |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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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 |
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1799134564617027584 |