CCN2 Increases TGF- Receptor Type II Expression in Vascular Smooth Muscle Cells: Essential Role of CCN2 in the TGF- Pathway Regulation

The cellular communication network factor 2 (CCN2/CTGF) has been traditionally described as a mediator of the fibrotic responses induced by other factors including the transforming growth factor (TGF- ). However, several studies have defined a direct role of CCN2 acting as a growth factor inducing o...

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Autores: Tejera-Muñoz, Antonio, Márquez-Expósito, Laura, Tejedor-Santamaría, Lucía, Rayego-Mateos, Sandra, Orejudo, Macarena, Suárez-Álvarez, Beatriz, López-Larrea, Carlos, Ruiz-Ortega, Marta, Rodrigues-Díez, Raul R.
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad Camilo José Cela (UCJC)
Repositorio:Depósito Digital e-UCJC
OAI Identifier:oai:repositorio.ucjc.edu:20.500.12020/1475
Acceso en línea:http://hdl.handle.net/20.500.12020/1475
https://doi.org/10.3390/ijms23010375
Access Level:acceso abierto
Palabra clave:Biología Celular y Molecular
CCN2
TGF
SMAD
TGF- receptors
EGFR
CTGF
3209 Farmacología
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spelling CCN2 Increases TGF- Receptor Type II Expression in Vascular Smooth Muscle Cells: Essential Role of CCN2 in the TGF- Pathway RegulationTejera-Muñoz, AntonioMárquez-Expósito, LauraTejedor-Santamaría, LucíaRayego-Mateos, SandraOrejudo, MacarenaSuárez-Álvarez, BeatrizLópez-Larrea, CarlosRuiz-Ortega, MartaRodrigues-Díez, Raul R.Biología Celular y MolecularCCN2TGFSMADTGF- receptorsEGFRCTGF3209 FarmacologíaThe cellular communication network factor 2 (CCN2/CTGF) has been traditionally described as a mediator of the fibrotic responses induced by other factors including the transforming growth factor (TGF- ). However, several studies have defined a direct role of CCN2 acting as a growth factor inducing oxidative and proinflammatory responses. The presence of CCN2 and TGF- together in the cellular context has been described as a requisite to induce a persistent fibrotic response, but the precise mechanisms implicated in this relation are not described yet. Considering the main role of TGF- receptors (T R) in the TGF- pathway activation, our aim was to investigate the effects of CCN2 in the regulation of T RI and T RII levels in vascular smooth muscle cells (VSMCs). While no differences were observed in T RI levels, an increase in T RII expression at both gene and protein level were found 48 h after stimulation with the C-terminal fragment of CCN2 (CCN2(IV)). Cell pretreatment with a T RI inhibitor did not modify T RII increment induced by CCN2(VI), demonstrating a TGF- -independent response. Secondly, CCN2(IV) rapidly activated the SMAD pathway in VSMCs, this being crucial in the upregulation of T RII since the preincubation with an SMAD3 inhibitor prevented it. Similarly, pretreatment with the epidermal growth factor receptor (EGFR) inhibitor erlotinib abolished T RII upregulation, indicating the participation of this receptor in the observed responses. Our findings suggest a direct role of CCN2 maintaining the TGF- pathway activation by increasing T RII expression in an EGFR-SMAD dependent manner activation.MDPI2021info:eu-repo/semantics/articlehttp://hdl.handle.net/20.500.12020/1475https://doi.org/10.3390/ijms23010375reponame:Depósito Digital e-UCJCinstname:Universidad Camilo José Cela (UCJC)Inglésinfo:eu-repo/semantics/openAccessoai:repositorio.ucjc.edu:20.500.12020/14752026-05-27T07:36:51Z
dc.title.none.fl_str_mv CCN2 Increases TGF- Receptor Type II Expression in Vascular Smooth Muscle Cells: Essential Role of CCN2 in the TGF- Pathway Regulation
title CCN2 Increases TGF- Receptor Type II Expression in Vascular Smooth Muscle Cells: Essential Role of CCN2 in the TGF- Pathway Regulation
spellingShingle CCN2 Increases TGF- Receptor Type II Expression in Vascular Smooth Muscle Cells: Essential Role of CCN2 in the TGF- Pathway Regulation
Tejera-Muñoz, Antonio
Biología Celular y Molecular
CCN2
TGF
SMAD
TGF- receptors
EGFR
CTGF
3209 Farmacología
title_short CCN2 Increases TGF- Receptor Type II Expression in Vascular Smooth Muscle Cells: Essential Role of CCN2 in the TGF- Pathway Regulation
title_full CCN2 Increases TGF- Receptor Type II Expression in Vascular Smooth Muscle Cells: Essential Role of CCN2 in the TGF- Pathway Regulation
title_fullStr CCN2 Increases TGF- Receptor Type II Expression in Vascular Smooth Muscle Cells: Essential Role of CCN2 in the TGF- Pathway Regulation
title_full_unstemmed CCN2 Increases TGF- Receptor Type II Expression in Vascular Smooth Muscle Cells: Essential Role of CCN2 in the TGF- Pathway Regulation
title_sort CCN2 Increases TGF- Receptor Type II Expression in Vascular Smooth Muscle Cells: Essential Role of CCN2 in the TGF- Pathway Regulation
dc.creator.none.fl_str_mv Tejera-Muñoz, Antonio
Márquez-Expósito, Laura
Tejedor-Santamaría, Lucía
Rayego-Mateos, Sandra
Orejudo, Macarena
Suárez-Álvarez, Beatriz
López-Larrea, Carlos
Ruiz-Ortega, Marta
Rodrigues-Díez, Raul R.
author Tejera-Muñoz, Antonio
author_facet Tejera-Muñoz, Antonio
Márquez-Expósito, Laura
Tejedor-Santamaría, Lucía
Rayego-Mateos, Sandra
Orejudo, Macarena
Suárez-Álvarez, Beatriz
López-Larrea, Carlos
Ruiz-Ortega, Marta
Rodrigues-Díez, Raul R.
author_role author
author2 Márquez-Expósito, Laura
Tejedor-Santamaría, Lucía
Rayego-Mateos, Sandra
Orejudo, Macarena
Suárez-Álvarez, Beatriz
López-Larrea, Carlos
Ruiz-Ortega, Marta
Rodrigues-Díez, Raul R.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Biología Celular y Molecular
CCN2
TGF
SMAD
TGF- receptors
EGFR
CTGF
3209 Farmacología
topic Biología Celular y Molecular
CCN2
TGF
SMAD
TGF- receptors
EGFR
CTGF
3209 Farmacología
description The cellular communication network factor 2 (CCN2/CTGF) has been traditionally described as a mediator of the fibrotic responses induced by other factors including the transforming growth factor (TGF- ). However, several studies have defined a direct role of CCN2 acting as a growth factor inducing oxidative and proinflammatory responses. The presence of CCN2 and TGF- together in the cellular context has been described as a requisite to induce a persistent fibrotic response, but the precise mechanisms implicated in this relation are not described yet. Considering the main role of TGF- receptors (T R) in the TGF- pathway activation, our aim was to investigate the effects of CCN2 in the regulation of T RI and T RII levels in vascular smooth muscle cells (VSMCs). While no differences were observed in T RI levels, an increase in T RII expression at both gene and protein level were found 48 h after stimulation with the C-terminal fragment of CCN2 (CCN2(IV)). Cell pretreatment with a T RI inhibitor did not modify T RII increment induced by CCN2(VI), demonstrating a TGF- -independent response. Secondly, CCN2(IV) rapidly activated the SMAD pathway in VSMCs, this being crucial in the upregulation of T RII since the preincubation with an SMAD3 inhibitor prevented it. Similarly, pretreatment with the epidermal growth factor receptor (EGFR) inhibitor erlotinib abolished T RII upregulation, indicating the participation of this receptor in the observed responses. Our findings suggest a direct role of CCN2 maintaining the TGF- pathway activation by increasing T RII expression in an EGFR-SMAD dependent manner activation.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12020/1475
https://doi.org/10.3390/ijms23010375
url http://hdl.handle.net/20.500.12020/1475
https://doi.org/10.3390/ijms23010375
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Depósito Digital e-UCJC
instname:Universidad Camilo José Cela (UCJC)
instname_str Universidad Camilo José Cela (UCJC)
reponame_str Depósito Digital e-UCJC
collection Depósito Digital e-UCJC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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