Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1

Autores
Barcelona, Pablo Federico; Jaldín Fincati, Javier Roberto; Sanchez, Maria Cecilia; Chiabrando, Gustavo Alberto
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In retinal proliferative diseases, Müller glial cells (MGCs) acquire migratory abilities. However, the mechanisms that regulate this migration remain poorly understood. In addition, proliferative disorders associated with enhanced activities of matrix metalloprotease 2 (MMP-2) and MMP-9 also present increased levels of the protease inhibitor α2-macroglobulin (α2M) and its receptor, the low-density lipoprotein receptor-related protein 1 (LRP1). In the present work, we investigated whether the protease activated form of α2M, α2M*, and LRP1 are involved with the MGC migratory process. By performing wound-scratch migration and zymography assays, we demonstrated that α2M* induced cell migration and proMMP-2 activation in the human Müller glial cell line, MIO-M1. This induction was blocked when LRP1 and MT1-MMP were knocked down with siRNA techniques. Using fluorescence microscopy and biochemical procedures, we found that α2M* induced an increase in LRP1 and MT1-MMP accumulation in early endosomes, followed by endocytic recycling and intracellular distribution of MT1-MMP toward cellular protrusions. Moreover, Rab11-dominant negative mutant abrogated MT1-MMP recycling pathway, cell migration, and proMMP-2 activation induced by α2M*. In conclusion, α2M*, through its receptor LRP1, induces cellular migration of Müller glial cells by a mechanism that involves MT1-MMP intracellular traffic to the plasma membrane by a Rab11-dependent recycling pathway.—Barcelona, P. F., Jaldín-Fincati, J. R., Sánchez, M. C., Chiabrando, G. A. Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1.
Fil: Barcelona, Pablo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Jaldín Fincati, Javier Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Sanchez, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Chiabrando, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Materia
Endocytosis
Intracellular Traffic
Proteases
Retina
Retinopathies
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/25016
Acceder
id CONICETDig_677b595200da46e9245e6d42986b8496
oai_identifier_str oai:ri.conicet.gov.ar:11336/25016
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1Barcelona, Pablo FedericoJaldín Fincati, Javier RobertoSanchez, Maria CeciliaChiabrando, Gustavo AlbertoEndocytosisIntracellular TrafficProteasesRetinaRetinopathieshttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3https://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1In retinal proliferative diseases, Müller glial cells (MGCs) acquire migratory abilities. However, the mechanisms that regulate this migration remain poorly understood. In addition, proliferative disorders associated with enhanced activities of matrix metalloprotease 2 (MMP-2) and MMP-9 also present increased levels of the protease inhibitor α2-macroglobulin (α2M) and its receptor, the low-density lipoprotein receptor-related protein 1 (LRP1). In the present work, we investigated whether the protease activated form of α2M, α2M*, and LRP1 are involved with the MGC migratory process. By performing wound-scratch migration and zymography assays, we demonstrated that α2M* induced cell migration and proMMP-2 activation in the human Müller glial cell line, MIO-M1. This induction was blocked when LRP1 and MT1-MMP were knocked down with siRNA techniques. Using fluorescence microscopy and biochemical procedures, we found that α2M* induced an increase in LRP1 and MT1-MMP accumulation in early endosomes, followed by endocytic recycling and intracellular distribution of MT1-MMP toward cellular protrusions. Moreover, Rab11-dominant negative mutant abrogated MT1-MMP recycling pathway, cell migration, and proMMP-2 activation induced by α2M*. In conclusion, α2M*, through its receptor LRP1, induces cellular migration of Müller glial cells by a mechanism that involves MT1-MMP intracellular traffic to the plasma membrane by a Rab11-dependent recycling pathway.—Barcelona, P. F., Jaldín-Fincati, J. R., Sánchez, M. C., Chiabrando, G. A. Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1.Fil: Barcelona, Pablo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Jaldín Fincati, Javier Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Sanchez, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Chiabrando, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFederation of American Societies for Experimental Biology2013-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/25016Barcelona, Pablo Federico; Jaldín Fincati, Javier Roberto; Sanchez, Maria Cecilia; Chiabrando, Gustavo Alberto; Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1; Federation of American Societies for Experimental Biology; Faseb Journal; 27; 8; 5-2013; 3181-31970892-6638CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1096/fj.12-221598info:eu-repo/semantics/altIdentifier/url/http://www.fasebj.org/content/27/8/3181info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:47:13Zoai:ri.conicet.gov.ar:11336/25016instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:47:13.404CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1
title Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1
spellingShingle Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1
Barcelona, Pablo Federico
Endocytosis
Intracellular Traffic
Proteases
Retina
Retinopathies
title_short Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1
title_full Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1
title_fullStr Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1
title_full_unstemmed Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1
title_sort Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1
dc.creator.none.fl_str_mv Barcelona, Pablo Federico
Jaldín Fincati, Javier Roberto
Sanchez, Maria Cecilia
Chiabrando, Gustavo Alberto
author Barcelona, Pablo Federico
author_facet Barcelona, Pablo Federico
Jaldín Fincati, Javier Roberto
Sanchez, Maria Cecilia
Chiabrando, Gustavo Alberto
author_role author
author2 Jaldín Fincati, Javier Roberto
Sanchez, Maria Cecilia
Chiabrando, Gustavo Alberto
author2_role author
author
author
dc.subject.none.fl_str_mv Endocytosis
Intracellular Traffic
Proteases
Retina
Retinopathies
topic Endocytosis
Intracellular Traffic
Proteases
Retina
Retinopathies
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In retinal proliferative diseases, Müller glial cells (MGCs) acquire migratory abilities. However, the mechanisms that regulate this migration remain poorly understood. In addition, proliferative disorders associated with enhanced activities of matrix metalloprotease 2 (MMP-2) and MMP-9 also present increased levels of the protease inhibitor α2-macroglobulin (α2M) and its receptor, the low-density lipoprotein receptor-related protein 1 (LRP1). In the present work, we investigated whether the protease activated form of α2M, α2M*, and LRP1 are involved with the MGC migratory process. By performing wound-scratch migration and zymography assays, we demonstrated that α2M* induced cell migration and proMMP-2 activation in the human Müller glial cell line, MIO-M1. This induction was blocked when LRP1 and MT1-MMP were knocked down with siRNA techniques. Using fluorescence microscopy and biochemical procedures, we found that α2M* induced an increase in LRP1 and MT1-MMP accumulation in early endosomes, followed by endocytic recycling and intracellular distribution of MT1-MMP toward cellular protrusions. Moreover, Rab11-dominant negative mutant abrogated MT1-MMP recycling pathway, cell migration, and proMMP-2 activation induced by α2M*. In conclusion, α2M*, through its receptor LRP1, induces cellular migration of Müller glial cells by a mechanism that involves MT1-MMP intracellular traffic to the plasma membrane by a Rab11-dependent recycling pathway.—Barcelona, P. F., Jaldín-Fincati, J. R., Sánchez, M. C., Chiabrando, G. A. Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1.
Fil: Barcelona, Pablo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Jaldín Fincati, Javier Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Sanchez, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Chiabrando, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
description In retinal proliferative diseases, Müller glial cells (MGCs) acquire migratory abilities. However, the mechanisms that regulate this migration remain poorly understood. In addition, proliferative disorders associated with enhanced activities of matrix metalloprotease 2 (MMP-2) and MMP-9 also present increased levels of the protease inhibitor α2-macroglobulin (α2M) and its receptor, the low-density lipoprotein receptor-related protein 1 (LRP1). In the present work, we investigated whether the protease activated form of α2M, α2M*, and LRP1 are involved with the MGC migratory process. By performing wound-scratch migration and zymography assays, we demonstrated that α2M* induced cell migration and proMMP-2 activation in the human Müller glial cell line, MIO-M1. This induction was blocked when LRP1 and MT1-MMP were knocked down with siRNA techniques. Using fluorescence microscopy and biochemical procedures, we found that α2M* induced an increase in LRP1 and MT1-MMP accumulation in early endosomes, followed by endocytic recycling and intracellular distribution of MT1-MMP toward cellular protrusions. Moreover, Rab11-dominant negative mutant abrogated MT1-MMP recycling pathway, cell migration, and proMMP-2 activation induced by α2M*. In conclusion, α2M*, through its receptor LRP1, induces cellular migration of Müller glial cells by a mechanism that involves MT1-MMP intracellular traffic to the plasma membrane by a Rab11-dependent recycling pathway.—Barcelona, P. F., Jaldín-Fincati, J. R., Sánchez, M. C., Chiabrando, G. A. Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1.
publishDate 2013
dc.date.none.fl_str_mv 2013-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/25016
Barcelona, Pablo Federico; Jaldín Fincati, Javier Roberto; Sanchez, Maria Cecilia; Chiabrando, Gustavo Alberto; Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1; Federation of American Societies for Experimental Biology; Faseb Journal; 27; 8; 5-2013; 3181-3197
0892-6638
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25016
identifier_str_mv Barcelona, Pablo Federico; Jaldín Fincati, Javier Roberto; Sanchez, Maria Cecilia; Chiabrando, Gustavo Alberto; Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1; Federation of American Societies for Experimental Biology; Faseb Journal; 27; 8; 5-2013; 3181-3197
0892-6638
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1096/fj.12-221598
info:eu-repo/semantics/altIdentifier/url/http://www.fasebj.org/content/27/8/3181
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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