The role of extracellular matrix stiffness in megakaryocyte and platelet development and function.
Fiche publication
Date publication
mars 2018
Journal
American journal of hematology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GACHET Christian, Dr MANGIN Pierre
Tous les auteurs :
Leiva O, Leon C, Kah Ng S, Mangin P, Gachet C, Ravid K
Lien Pubmed
Résumé
The extracellular matrix (ECM) is a key acellular structure in constant remodeling to provide tissue cohesion and rigidity. Deregulation of the balance between matrix deposition, degradation, and crosslinking results in fibrosis. Bone marrow fibrosis (BMF) is associated with several malignant and nonmalignant pathologies severely affecting blood cell production. BMF results from abnormal deposition of collagen fibers and enhanced lysyl oxidase-mediated ECM crosslinking within the marrow, thereby increasing marrow stiffness. Bone marrow stiffness has been recently recognized as an important regulator of blood cell development, notably by modifying the fate and differentiation process of hematopoietic or mesenchymal stem cells. This review surveys the different components of the ECM and their influence on stem cell development, with a focus on the impact of the ECM composition and stiffness on the megakaryocytic lineage in health and disease. Megakaryocyte maturation and the biogenesis of their progeny, the platelets, are thought to respond to environmental mechanical forces through a number of mechanosensors, including integrins and mechanosensitive ion channels, reviewed here.
Référence
Am. J. Hematol.. 2018 Mar;93(3):430-441