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A new path to platelet production through matrix sensing.
- Source :
-
Haematologica [Haematologica] 2017 Jul; Vol. 102 (7), pp. 1150-1160. Date of Electronic Publication: 2017 Apr 14. - Publication Year :
- 2017
-
Abstract
- Megakaryocytes (MK) in the bone marrow (BM) are immersed in a network of extracellular matrix components that regulates platelet release into the circulation. Combining biological and bioengineering approaches, we found that the activation of transient receptor potential cation channel subfamily V member 4 (TRPV4), a mechano-sensitive ion channel, is induced upon MK adhesion on softer matrices. This response promoted platelet production by triggering a cascade of events that lead to calcium influx, β1 integrin activation and internalization, and Akt phosphorylation, responses not found on stiffer matrices. Lysyl oxidase (LOX) is a physiological modulator of BM matrix stiffness via collagen crosslinking. In vivo inhibition of LOX and consequent matrix softening lead to TRPV4 activation cascade and increased platelet levels. At the same time, in vitro proplatelet formation was reduced on a recombinant enzyme-mediated stiffer collagen. These results suggest a novel mechanism by which MKs, through TRPV4, sense extracellular matrix environmental rigidity and release platelets accordingly.<br /> (Copyright© 2017 Ferrata Storti Foundation.)
- Subjects :
- Animals
Calcium metabolism
Cell Adhesion
Cell Differentiation
Collagen Type I metabolism
Collagen Type IV metabolism
Hematopoietic Stem Cells cytology
Hematopoietic Stem Cells metabolism
Humans
Integrin beta1 metabolism
Mice
Phosphatidylinositol 3-Kinases metabolism
Protein Transport
Protein-Lysine 6-Oxidase metabolism
Proto-Oncogene Proteins c-akt metabolism
TRPV Cation Channels metabolism
Blood Platelets cytology
Blood Platelets metabolism
Megakaryocytes cytology
Megakaryocytes metabolism
Thrombopoiesis
Subjects
Details
- Language :
- English
- ISSN :
- 1592-8721
- Volume :
- 102
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Haematologica
- Publication Type :
- Academic Journal
- Accession number :
- 28411253
- Full Text :
- https://doi.org/10.3324/haematol.2016.161562