The basement membrane protein nidogen-1 supports platelet adhesion and activation

Hari Hara Sudhan Lakshmanan, Alexander R. Melrose, Anna Liisa I. Sepp, Annachiara Mitrugno, Anh T.P. Ngo, Ayesha Khader, Rachel Thompson, Daniel Sallee, Jiaqing Pang, Pierre H. Mangin, Martine Jandrot-Perrus, Joseph E. Aslan, Owen J.T. McCarty

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The core structure of the extracellular basement membrane is made up of self-assembling networks of collagen and laminin which associate with each other through the bridging adapter proteins including the sulfated monomeric glycoprotein nidogen. While collagen and laminin are known to support platelet adhesion and activation via β1 integrins and glycoprotein (GP) VI, respectively, whether nidogen contributes to platelet activation and hemostasis is unknown. In this study, we demonstrate that recombinant human nidogen-1 supports platelet adhesion and stimulates platelet activation in a phospholipase-C γ-2 (PLCγ2), Src and Syk kinase-dependent manner downstream. Platetet adhesion to nidogen-1 was inhibited by blocking the platelet receptors GPVI and β1 integrins. Platelet adhesion to nidogen-1 activated the IκB kinase (IKK) complex, while pharmacological inhibition of IKK blocked platelet spreading on nidogen. Taken together our results suggest that nidogen may play a redundant role in hemostasis by activating platelets downstream of GPVI.

Original languageEnglish (US)
Pages (from-to)424-428
Number of pages5
JournalPlatelets
Volume32
Issue number3
DOIs
StatePublished - 2021

Keywords

  • Extracellular matrix proteins
  • hemostasis
  • nidogen
  • platelet

ASJC Scopus subject areas

  • Hematology

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