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Adrenomedullin increases fibroblast-like synoviocyte adhesion to extracellular matrix proteins by upregulating integrin activation
INTRODUCTION: Rheumatoid arthritis (RA) is characterized by bone and cartilage invasion by fibroblast-like synoviocytes (FLSs). Adrenomedullin, a peptide with anabolic and antiapoptotic properties, is secreted by rheumatoid FLSs. Adrenomedullin also increases the expression of adhesion molecules in...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991025/ https://www.ncbi.nlm.nih.gov/pubmed/20942979 http://dx.doi.org/10.1186/ar3160 |
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author | Ah Kioon, Marie-Dominique Asensio, Carine Ea, Hang-Korng Uzan, Benjamin Cohen-Solal, Martine Lioté, Frédéric |
author_facet | Ah Kioon, Marie-Dominique Asensio, Carine Ea, Hang-Korng Uzan, Benjamin Cohen-Solal, Martine Lioté, Frédéric |
author_sort | Ah Kioon, Marie-Dominique |
collection | PubMed |
description | INTRODUCTION: Rheumatoid arthritis (RA) is characterized by bone and cartilage invasion by fibroblast-like synoviocytes (FLSs). Adrenomedullin, a peptide with anabolic and antiapoptotic properties, is secreted by rheumatoid FLSs. Adrenomedullin also increases the expression of adhesion molecules in endothelial cells and keratinocytes. Here, we investigated whether adrenomedullin mediated FLS adhesion to extracellular matrix (ECM) proteins. METHODS: FLSs were isolated from synovial tissues from RA and osteoarthritis (OA) patients. Plates were coated overnight with the ECM proteins vitronectin, fibronectin, and type I collagen (Coll.I). Adrenomedullin was used as a soluble FLS ligand before plating. We tested interactions with the adrenomedullin receptor antagonist (22-52)adrenomedullin and with the protein kinase A (PKA) inhibitor H-89, and inhibition of co-receptor RAMP-2 by siRNA. Cell adhesion was measured by using color densitometry. Activation of α(2 )and β(1 )integrins was evaluated by fluorescent microscopy; integrin inhibition, by RGD peptides; and the talin-integrin interaction, by immunoprecipitation (IP). RESULTS: Adrenomedullin specifically increased RA-FLS adhesion to vitronectin, fibronectin, and Coll.I; no such effect was found for OA-FLS adhesion. Basal or adrenomedullin-stimulated RA-FLS adhesion was inhibited by (22-52)adrenomedullin, H-89, and RAMP-2 siRNA. Adrenomedullin-stimulated adhesion was inhibited by RGD peptides, and associated with α(2 )and β(1 )integrin activation. This activation was shown with IP to be related to an integrin-talin interaction and was significantly decreased by (22-52)adrenomedullin. CONCLUSIONS: Adrenomedullin-stimulated RA-FLS adhesion was specific for ECM proteins and mediated by α(2 )and β(1 )integrins. This effect of adrenomedullin was dependent on adrenomedullin receptors. These results support a new role for adrenomedullin in rheumatoid synovial fibroblast pathobiology. |
format | Text |
id | pubmed-2991025 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-29910252010-11-25 Adrenomedullin increases fibroblast-like synoviocyte adhesion to extracellular matrix proteins by upregulating integrin activation Ah Kioon, Marie-Dominique Asensio, Carine Ea, Hang-Korng Uzan, Benjamin Cohen-Solal, Martine Lioté, Frédéric Arthritis Res Ther Research Article INTRODUCTION: Rheumatoid arthritis (RA) is characterized by bone and cartilage invasion by fibroblast-like synoviocytes (FLSs). Adrenomedullin, a peptide with anabolic and antiapoptotic properties, is secreted by rheumatoid FLSs. Adrenomedullin also increases the expression of adhesion molecules in endothelial cells and keratinocytes. Here, we investigated whether adrenomedullin mediated FLS adhesion to extracellular matrix (ECM) proteins. METHODS: FLSs were isolated from synovial tissues from RA and osteoarthritis (OA) patients. Plates were coated overnight with the ECM proteins vitronectin, fibronectin, and type I collagen (Coll.I). Adrenomedullin was used as a soluble FLS ligand before plating. We tested interactions with the adrenomedullin receptor antagonist (22-52)adrenomedullin and with the protein kinase A (PKA) inhibitor H-89, and inhibition of co-receptor RAMP-2 by siRNA. Cell adhesion was measured by using color densitometry. Activation of α(2 )and β(1 )integrins was evaluated by fluorescent microscopy; integrin inhibition, by RGD peptides; and the talin-integrin interaction, by immunoprecipitation (IP). RESULTS: Adrenomedullin specifically increased RA-FLS adhesion to vitronectin, fibronectin, and Coll.I; no such effect was found for OA-FLS adhesion. Basal or adrenomedullin-stimulated RA-FLS adhesion was inhibited by (22-52)adrenomedullin, H-89, and RAMP-2 siRNA. Adrenomedullin-stimulated adhesion was inhibited by RGD peptides, and associated with α(2 )and β(1 )integrin activation. This activation was shown with IP to be related to an integrin-talin interaction and was significantly decreased by (22-52)adrenomedullin. CONCLUSIONS: Adrenomedullin-stimulated RA-FLS adhesion was specific for ECM proteins and mediated by α(2 )and β(1 )integrins. This effect of adrenomedullin was dependent on adrenomedullin receptors. These results support a new role for adrenomedullin in rheumatoid synovial fibroblast pathobiology. BioMed Central 2010 2010-10-14 /pmc/articles/PMC2991025/ /pubmed/20942979 http://dx.doi.org/10.1186/ar3160 Text en Copyright ©2010 Lioté et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited |
spellingShingle | Research Article Ah Kioon, Marie-Dominique Asensio, Carine Ea, Hang-Korng Uzan, Benjamin Cohen-Solal, Martine Lioté, Frédéric Adrenomedullin increases fibroblast-like synoviocyte adhesion to extracellular matrix proteins by upregulating integrin activation |
title | Adrenomedullin increases fibroblast-like synoviocyte adhesion to extracellular matrix proteins by upregulating integrin activation |
title_full | Adrenomedullin increases fibroblast-like synoviocyte adhesion to extracellular matrix proteins by upregulating integrin activation |
title_fullStr | Adrenomedullin increases fibroblast-like synoviocyte adhesion to extracellular matrix proteins by upregulating integrin activation |
title_full_unstemmed | Adrenomedullin increases fibroblast-like synoviocyte adhesion to extracellular matrix proteins by upregulating integrin activation |
title_short | Adrenomedullin increases fibroblast-like synoviocyte adhesion to extracellular matrix proteins by upregulating integrin activation |
title_sort | adrenomedullin increases fibroblast-like synoviocyte adhesion to extracellular matrix proteins by upregulating integrin activation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991025/ https://www.ncbi.nlm.nih.gov/pubmed/20942979 http://dx.doi.org/10.1186/ar3160 |
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