@article{1481f8f0f5fe409fb9454729ddc7eb22,
title = "The basement membrane protein nidogen-1 supports platelet adhesion and activation",
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.",
keywords = "Extracellular matrix proteins, hemostasis, nidogen, platelet",
author = "Lakshmanan, {Hari Hara Sudhan} and Melrose, {Alexander R.} and Sepp, {Anna Liisa I.} and Annachiara Mitrugno and Ngo, {Anh T.P.} and Ayesha Khader and Rachel Thompson and Daniel Sallee and Jiaqing Pang and Mangin, {Pierre H.} and Martine Jandrot-Perrus and Aslan, {Joseph E.} and McCarty, {Owen J.T.}",
note = "Funding Information: This work was supported by the American Heart Association [18UFEL33960363]; National Institutes of Health [R01GM116184, R01HL101972, R01HL144113]. This work was supported by grants from the National Institutes of Health (R01HL146549 to J. Aslan and R01HL101972, R01HL144113, and R01GM116184 to O. McCarty) and the American Heart Association (18UFEL33960363 to O. McCarty). A. Sepp and A. Khader are Oregon State University Johnson Scholars. R. Thompson is an AHA Undergraduate Research Fellow. Funding Information: This work was supported by grants from the National Institutes of Health (R01HL146549 to J. Aslan and R01HL101972, R01HL144113, and R01GM116184 to O. McCarty) and the American Heart Association (18UFEL33960363 to O. McCarty). A. Sepp and A. Khader are Oregon State University Johnson Scholars. R. Thompson is an AHA Undergraduate Research Fellow. Publisher Copyright: {\textcopyright} 2020 Taylor & Francis Group, LLC.",
year = "2021",
doi = "10.1080/09537104.2020.1745170",
language = "English (US)",
volume = "32",
pages = "424--428",
journal = "Platelets",
issn = "0953-7104",
publisher = "Informa Healthcare",
number = "3",
}