RANTES/CCL5 mediated-biological effects depend on the syndecan-4/PKCα signaling pathway
The perpetuation of angiogenesis is involved in certain chronic inflammatory diseases. The accelerated neovascularisation may result from an inflammatory status with a response of both endothelial cells and monocytes to inflammatory mediators such as chemokines. We have previously described in vitro...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2014-09-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/3/10/995 |
| _version_ | 1818663278432223232 |
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| author | Loïc Maillard Naoaki Saito Hanna Hlawaty Véronique Friand Nadine Suffee Fanny Chmilewsky Oualid Haddad Christelle Laguillier Erwan Guyot Takehiko Ueyama Olivier Oudar Angela Sutton Nathalie Charnaux |
| author_facet | Loïc Maillard Naoaki Saito Hanna Hlawaty Véronique Friand Nadine Suffee Fanny Chmilewsky Oualid Haddad Christelle Laguillier Erwan Guyot Takehiko Ueyama Olivier Oudar Angela Sutton Nathalie Charnaux |
| author_sort | Loïc Maillard |
| collection | DOAJ |
| description | The perpetuation of angiogenesis is involved in certain chronic inflammatory diseases. The accelerated neovascularisation may result from an inflammatory status with a response of both endothelial cells and monocytes to inflammatory mediators such as chemokines. We have previously described in vitro and in vivo the pro-angiogenic effects of the chemokine Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES)/CCL5. The effects of RANTES/CCL5 may be related to its binding to G protein-coupled receptors and to proteoglycans such as syndecan-1 and -4. The aim of this study was to evaluate the functionality of syndecan-4 as a co-receptor of RANTES/CCL5 by the use of mutated syndecan-4 constructs. Our data demonstrate that site-directed mutations in syndecan-4 modify RANTES/CCL5 biological activities in endothelial cells. The SDC4S179A mutant, associated with an induced protein kinase C (PKC)α activation, leads to higher RANTES/CCL5 pro-angiogenic effects, whereas the SDC4L188QQ and the SDC4A198del mutants, leading to lower phosphatidylinositol 4,5-bisphosphate (PIP2) binding or to lower PDZ protein binding respectively, are associated with reduced RANTES/CCL5 cellular effects. Moreover, our data highlight that the intracellular domain of SDC-4 is involved in RANTES/CCL5-induced activation of the PKCα signaling pathway and biological effect. As RANTES/CCL5 is involved in various physiopathological processes, the development of a new therapeutic strategy may be reliant on the mechanism by which RANTES/CCL5 exerts its biological activities, for example by targeting the binding of the chemokine to its proteoglycan receptor. |
| first_indexed | 2024-12-17T05:14:18Z |
| format | Article |
| id | doaj.art-270ce84ec53548b88673fcc443cfd1b3 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-17T05:14:18Z |
| publishDate | 2014-09-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-270ce84ec53548b88673fcc443cfd1b32022-12-21T22:02:10ZengThe Company of BiologistsBiology Open2046-63902014-09-01310995100410.1242/bio.2014822720148227RANTES/CCL5 mediated-biological effects depend on the syndecan-4/PKCα signaling pathwayLoïc Maillard0Naoaki Saito1Hanna Hlawaty2Véronique Friand3Nadine Suffee4Fanny Chmilewsky5Oualid Haddad6Christelle Laguillier7Erwan Guyot8Takehiko Ueyama9Olivier Oudar10Angela Sutton11Nathalie Charnaux12 Inserm U1148, Laboratory for Vascular Translational Science, Bio-ingénierie Cardio-vasculaire, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, 74 rue Marcel Cachin, 93017 Bobigny, France Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, Kobe 657-8501, Japan Inserm U1148, Laboratory for Vascular Translational Science, Bio-ingénierie Cardio-vasculaire, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, 74 rue Marcel Cachin, 93017 Bobigny, France Inserm U1148, Laboratory for Vascular Translational Science, Bio-ingénierie Cardio-vasculaire, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, 74 rue Marcel Cachin, 93017 Bobigny, France Inserm U1148, Laboratory for Vascular Translational Science, Bio-ingénierie Cardio-vasculaire, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, 74 rue Marcel Cachin, 93017 Bobigny, France Inserm U1148, Laboratory for Vascular Translational Science, Bio-ingénierie Cardio-vasculaire, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, 74 rue Marcel Cachin, 93017 Bobigny, France Inserm U1148, Laboratory for Vascular Translational Science, Bio-ingénierie Cardio-vasculaire, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, 74 rue Marcel Cachin, 93017 Bobigny, France Inserm U1148, Laboratory for Vascular Translational Science, Bio-ingénierie Cardio-vasculaire, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, 74 rue Marcel Cachin, 93017 Bobigny, France Inserm U1148, Laboratory for Vascular Translational Science, Bio-ingénierie Cardio-vasculaire, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, 74 rue Marcel Cachin, 93017 Bobigny, France Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, Kobe 657-8501, Japan Inserm U1148, Laboratory for Vascular Translational Science, Bio-ingénierie Cardio-vasculaire, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, 74 rue Marcel Cachin, 93017 Bobigny, France Inserm U1148, Laboratory for Vascular Translational Science, Bio-ingénierie Cardio-vasculaire, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, 74 rue Marcel Cachin, 93017 Bobigny, France Inserm U1148, Laboratory for Vascular Translational Science, Bio-ingénierie Cardio-vasculaire, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, 74 rue Marcel Cachin, 93017 Bobigny, France The perpetuation of angiogenesis is involved in certain chronic inflammatory diseases. The accelerated neovascularisation may result from an inflammatory status with a response of both endothelial cells and monocytes to inflammatory mediators such as chemokines. We have previously described in vitro and in vivo the pro-angiogenic effects of the chemokine Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES)/CCL5. The effects of RANTES/CCL5 may be related to its binding to G protein-coupled receptors and to proteoglycans such as syndecan-1 and -4. The aim of this study was to evaluate the functionality of syndecan-4 as a co-receptor of RANTES/CCL5 by the use of mutated syndecan-4 constructs. Our data demonstrate that site-directed mutations in syndecan-4 modify RANTES/CCL5 biological activities in endothelial cells. The SDC4S179A mutant, associated with an induced protein kinase C (PKC)α activation, leads to higher RANTES/CCL5 pro-angiogenic effects, whereas the SDC4L188QQ and the SDC4A198del mutants, leading to lower phosphatidylinositol 4,5-bisphosphate (PIP2) binding or to lower PDZ protein binding respectively, are associated with reduced RANTES/CCL5 cellular effects. Moreover, our data highlight that the intracellular domain of SDC-4 is involved in RANTES/CCL5-induced activation of the PKCα signaling pathway and biological effect. As RANTES/CCL5 is involved in various physiopathological processes, the development of a new therapeutic strategy may be reliant on the mechanism by which RANTES/CCL5 exerts its biological activities, for example by targeting the binding of the chemokine to its proteoglycan receptor.http://bio.biologists.org/content/3/10/995Syndecan-4ChemokinePKCRANTES/CCL5Endothelial cell |
| spellingShingle | Loïc Maillard Naoaki Saito Hanna Hlawaty Véronique Friand Nadine Suffee Fanny Chmilewsky Oualid Haddad Christelle Laguillier Erwan Guyot Takehiko Ueyama Olivier Oudar Angela Sutton Nathalie Charnaux RANTES/CCL5 mediated-biological effects depend on the syndecan-4/PKCα signaling pathway Biology Open Syndecan-4 Chemokine PKC RANTES/CCL5 Endothelial cell |
| title | RANTES/CCL5 mediated-biological effects depend on the syndecan-4/PKCα signaling pathway |
| title_full | RANTES/CCL5 mediated-biological effects depend on the syndecan-4/PKCα signaling pathway |
| title_fullStr | RANTES/CCL5 mediated-biological effects depend on the syndecan-4/PKCα signaling pathway |
| title_full_unstemmed | RANTES/CCL5 mediated-biological effects depend on the syndecan-4/PKCα signaling pathway |
| title_short | RANTES/CCL5 mediated-biological effects depend on the syndecan-4/PKCα signaling pathway |
| title_sort | rantes ccl5 mediated biological effects depend on the syndecan 4 pkcα signaling pathway |
| topic | Syndecan-4 Chemokine PKC RANTES/CCL5 Endothelial cell |
| url | http://bio.biologists.org/content/3/10/995 |
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