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

Lewis S C Ward, Lozan Sheriff, Jennifer L Marshall, Julia E Manning, Alexander Brill, Gerard B Nash, Helen M McGettrick

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)
305 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article numberjcs222067
Number of pages12
JournalJournal of Cell Science
Volume132
Issue number5
Early online date11 Feb 2019
DOIs
Publication statusPublished - 25 Feb 2019

Keywords

  • Endothelial cell
  • Mesenchymal stromal cell
  • Migration
  • Platelet
  • Podoplanin

ASJC Scopus subject areas

  • Cell Biology

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