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Podoplanin regulates the migration of mesenchymal stromal cells and their interaction with platelets

Mesenchymal stromal cells (MSCs) upregulate podoplanin at sites of infection, chronic inflammation and cancer. Here, we investigated the functional consequences of podoplanin expression on the migratory potential of MSCs and their interactions with circulating platelets. Expression of podoplanin sig...

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Autores principales: Ward, Lewis S. C., Sheriff, Lozan, Marshall, Jennifer L., Manning, Julia E., Brill, Alexander, Nash, Gerard B., McGettrick, Helen M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6432720/
https://www.ncbi.nlm.nih.gov/pubmed/30745334
http://dx.doi.org/10.1242/jcs.222067
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author Ward, Lewis S. C.
Sheriff, Lozan
Marshall, Jennifer L.
Manning, Julia E.
Brill, Alexander
Nash, Gerard B.
McGettrick, Helen M.
author_facet Ward, Lewis S. C.
Sheriff, Lozan
Marshall, Jennifer L.
Manning, Julia E.
Brill, Alexander
Nash, Gerard B.
McGettrick, Helen M.
author_sort Ward, Lewis S. C.
collection PubMed
description Mesenchymal stromal cells (MSCs) upregulate podoplanin at sites of infection, chronic inflammation and cancer. Here, we investigated the functional consequences of podoplanin expression on the migratory potential of MSCs and their interactions with circulating platelets. Expression of podoplanin significantly enhanced the migration of MSCs compared to MSCs lacking podoplanin. Rac-1 inhibition altered the membrane localisation of podoplanin and in turn significantly reduced MSC migration. Blocking Rac-1 activity had no effect on the migration of MSCs lacking podoplanin, indicating that it was responsible for regulation of migration through podoplanin. When podoplanin-expressing MSCs were seeded on the basal surface of a porous filter, they were able to capture platelets perfused over the uncoated apical surface and induce platelet aggregation. Similar microthrombi were observed when endothelial cells (ECs) were co-cultured on the apical surface. Confocal imaging shows podoplanin-expressing MSCs extending processes into the EC layer, and these processes could interact with circulating platelets. In both models, platelet aggregation induced by podoplanin-expressing MSCs was inhibited by treatment with recombinant soluble C-type lectin-like receptor 2 (CLEC-2; encoded by the gene Clec1b). Thus, podoplanin may enhance the migratory capacity of tissue-resident MSCs and enable novel interactions with cells expressing CLEC-2.
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spelling pubmed-64327202019-03-27 Podoplanin regulates the migration of mesenchymal stromal cells and their interaction with platelets Ward, Lewis S. C. Sheriff, Lozan Marshall, Jennifer L. Manning, Julia E. Brill, Alexander Nash, Gerard B. McGettrick, Helen M. J Cell Sci Research Article Mesenchymal stromal cells (MSCs) upregulate podoplanin at sites of infection, chronic inflammation and cancer. Here, we investigated the functional consequences of podoplanin expression on the migratory potential of MSCs and their interactions with circulating platelets. Expression of podoplanin significantly enhanced the migration of MSCs compared to MSCs lacking podoplanin. Rac-1 inhibition altered the membrane localisation of podoplanin and in turn significantly reduced MSC migration. Blocking Rac-1 activity had no effect on the migration of MSCs lacking podoplanin, indicating that it was responsible for regulation of migration through podoplanin. When podoplanin-expressing MSCs were seeded on the basal surface of a porous filter, they were able to capture platelets perfused over the uncoated apical surface and induce platelet aggregation. Similar microthrombi were observed when endothelial cells (ECs) were co-cultured on the apical surface. Confocal imaging shows podoplanin-expressing MSCs extending processes into the EC layer, and these processes could interact with circulating platelets. In both models, platelet aggregation induced by podoplanin-expressing MSCs was inhibited by treatment with recombinant soluble C-type lectin-like receptor 2 (CLEC-2; encoded by the gene Clec1b). Thus, podoplanin may enhance the migratory capacity of tissue-resident MSCs and enable novel interactions with cells expressing CLEC-2. The Company of Biologists Ltd 2019-03-01 2019-02-25 /pmc/articles/PMC6432720/ /pubmed/30745334 http://dx.doi.org/10.1242/jcs.222067 Text en © 2019. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Ward, Lewis S. C.
Sheriff, Lozan
Marshall, Jennifer L.
Manning, Julia E.
Brill, Alexander
Nash, Gerard B.
McGettrick, Helen M.
Podoplanin regulates the migration of mesenchymal stromal cells and their interaction with platelets
title Podoplanin regulates the migration of mesenchymal stromal cells and their interaction with platelets
title_full Podoplanin regulates the migration of mesenchymal stromal cells and their interaction with platelets
title_fullStr Podoplanin regulates the migration of mesenchymal stromal cells and their interaction with platelets
title_full_unstemmed Podoplanin regulates the migration of mesenchymal stromal cells and their interaction with platelets
title_short Podoplanin regulates the migration of mesenchymal stromal cells and their interaction with platelets
title_sort podoplanin regulates the migration of mesenchymal stromal cells and their interaction with platelets
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6432720/
https://www.ncbi.nlm.nih.gov/pubmed/30745334
http://dx.doi.org/10.1242/jcs.222067
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