CCN2 binds to tubular epithelial cells in the kidney

Cellular communication network-2 (CCN2), also called connective tissue growth factor (CTGF), is considered a fibrotic biomarker and has been suggested as a potential therapeutic target for kidney pathologies. CCN2 is a matricellular protein with four distinct structural modules that can exert a dual...

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Autores: Rayego-Mateos, Sandra, Morgado-Pascual, José Luis, Lavoz, Carolina, Rodrigues-Diez, Raul R., Márquez-Expósito, Laura, Tejera-Muñoz, Antonio, Tejedor Santamaria, Lucía, Rubio-Soto, Irene, Marchant Hernández, Vanessa Alejandra, Ruiz Ortega, Marta
Tipo de documento: artigo
Data de publicação:2022
País:España
Recursos:Universidad Autónoma de Madrid
Repositório:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglês
OAI Identifier:oai:repositorio.uam.es:10486/706789
Acesso em linha:http://hdl.handle.net/10486/706789
https://dx.doi.org/10.3390/biom12020252
Access Level:Acceso aberto
Palavra-chave:CCN2
CTGF
EGFR
Kidney damage
Medicina
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spelling CCN2 binds to tubular epithelial cells in the kidneyRayego-Mateos, SandraMorgado-Pascual, José LuisLavoz, CarolinaRodrigues-Diez, Raul R.Márquez-Expósito, LauraTejera-Muñoz, AntonioTejedor Santamaria, LucíaRubio-Soto, IreneMarchant Hernández, Vanessa AlejandraRuiz Ortega, MartaCCN2CTGFEGFRKidney damageMedicinaCellular communication network-2 (CCN2), also called connective tissue growth factor (CTGF), is considered a fibrotic biomarker and has been suggested as a potential therapeutic target for kidney pathologies. CCN2 is a matricellular protein with four distinct structural modules that can exert a dual function as a matricellular protein and as a growth factor. Previous experiments using surface plasmon resonance and cultured renal cells have demonstrated that the C-terminal module of CCN2 (CCN2(IV)) interacts with the epidermal growth factor receptor (EGFR). Moreover, CCN2(IV) activates proinflammatory and profibrotic responses in the mouse kidney. The aim of this paper was to locate the in vivo cellular CCN2/EGFR binding sites in the kidney. To this aim, the C-terminal module CCN2(IV) was labeled with a fluorophore (Cy5), and two different administration routes were employed. Both intraperitoneal and direct intra-renal injection of Cy5-CCN2(IV) in mice demonstrated that CCN2(IV) preferentially binds to the tubular epithelial cells, while no signal was detected in glomeruli. Moreover, co-localization of Cy5-CCN2(IV) binding and activated EGFR was found in tubules. In cultured tubular epithelial cells, live-cell confocal microscopy experiments showed that EGFR gene silencing blocked Cy5-CCN2(IV) binding to tubuloepithelial cells. These data clearly show the existence of CCN2/EGFR binding sites in the kidney, mainly in tubular epithelial cells. In conclusion, these studies show that circulating CCN2(IV) can directly bind and activate tubular cells, supporting the role of CCN2 as a growth factor involved in kidney damage progressionThis research was funded by grants from the Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union (PI17/00119, PI20/00140, and DTS20/00083), Sara Borrell’ program from Instituto de Salud Carlos III (ISCIII) (grant number CD20/00042 to R.R.R-D), Red de Investigación Renal REDINREN: RD16/0009 and RICORS program to RICORS2040 (RD21/0005) to M.R-O. Sociedad Española de Nefrología, “NOVELREN-CM: Enfermedad renal crónica: nuevas Estrategias para la prevención, Diagnóstico y tratamiento” (B2017/BMD-3751 to M.R.-O.), “Convocatoria Dinamización Europa Investigación 2019” MINECO (EIN2019-103294 to M.R.-O. and S.R.-M.), Juan de la Cierva formación grant: FJC2019-042028-I to J.L.M.-P., and Juan de la Cierva incorporación grant: IJC2018-035187-I to S.R.-MMDPIDepartamento de MedicinaFacultad de Medicina20222022-02-03research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/706789https://dx.doi.org/10.3390/biom12020252reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7067892026-06-23T12:46:27Z
dc.title.none.fl_str_mv CCN2 binds to tubular epithelial cells in the kidney
title CCN2 binds to tubular epithelial cells in the kidney
spellingShingle CCN2 binds to tubular epithelial cells in the kidney
Rayego-Mateos, Sandra
CCN2
CTGF
EGFR
Kidney damage
Medicina
title_short CCN2 binds to tubular epithelial cells in the kidney
title_full CCN2 binds to tubular epithelial cells in the kidney
title_fullStr CCN2 binds to tubular epithelial cells in the kidney
title_full_unstemmed CCN2 binds to tubular epithelial cells in the kidney
title_sort CCN2 binds to tubular epithelial cells in the kidney
dc.creator.none.fl_str_mv Rayego-Mateos, Sandra
Morgado-Pascual, José Luis
Lavoz, Carolina
Rodrigues-Diez, Raul R.
Márquez-Expósito, Laura
Tejera-Muñoz, Antonio
Tejedor Santamaria, Lucía
Rubio-Soto, Irene
Marchant Hernández, Vanessa Alejandra
Ruiz Ortega, Marta
author Rayego-Mateos, Sandra
author_facet Rayego-Mateos, Sandra
Morgado-Pascual, José Luis
Lavoz, Carolina
Rodrigues-Diez, Raul R.
Márquez-Expósito, Laura
Tejera-Muñoz, Antonio
Tejedor Santamaria, Lucía
Rubio-Soto, Irene
Marchant Hernández, Vanessa Alejandra
Ruiz Ortega, Marta
author_role author
author2 Morgado-Pascual, José Luis
Lavoz, Carolina
Rodrigues-Diez, Raul R.
Márquez-Expósito, Laura
Tejera-Muñoz, Antonio
Tejedor Santamaria, Lucía
Rubio-Soto, Irene
Marchant Hernández, Vanessa Alejandra
Ruiz Ortega, Marta
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Medicina
Facultad de Medicina
dc.subject.none.fl_str_mv CCN2
CTGF
EGFR
Kidney damage
Medicina
topic CCN2
CTGF
EGFR
Kidney damage
Medicina
description Cellular communication network-2 (CCN2), also called connective tissue growth factor (CTGF), is considered a fibrotic biomarker and has been suggested as a potential therapeutic target for kidney pathologies. CCN2 is a matricellular protein with four distinct structural modules that can exert a dual function as a matricellular protein and as a growth factor. Previous experiments using surface plasmon resonance and cultured renal cells have demonstrated that the C-terminal module of CCN2 (CCN2(IV)) interacts with the epidermal growth factor receptor (EGFR). Moreover, CCN2(IV) activates proinflammatory and profibrotic responses in the mouse kidney. The aim of this paper was to locate the in vivo cellular CCN2/EGFR binding sites in the kidney. To this aim, the C-terminal module CCN2(IV) was labeled with a fluorophore (Cy5), and two different administration routes were employed. Both intraperitoneal and direct intra-renal injection of Cy5-CCN2(IV) in mice demonstrated that CCN2(IV) preferentially binds to the tubular epithelial cells, while no signal was detected in glomeruli. Moreover, co-localization of Cy5-CCN2(IV) binding and activated EGFR was found in tubules. In cultured tubular epithelial cells, live-cell confocal microscopy experiments showed that EGFR gene silencing blocked Cy5-CCN2(IV) binding to tubuloepithelial cells. These data clearly show the existence of CCN2/EGFR binding sites in the kidney, mainly in tubular epithelial cells. In conclusion, these studies show that circulating CCN2(IV) can directly bind and activate tubular cells, supporting the role of CCN2 as a growth factor involved in kidney damage progression
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-02-03
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/706789
https://dx.doi.org/10.3390/biom12020252
url http://hdl.handle.net/10486/706789
https://dx.doi.org/10.3390/biom12020252
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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