Alan Nurden: Thyroid Hormones as Regulators of Acute Platelet Release
Alan Nurden, Emeritus Research Director at CNRS, Co-Founder of the French National Reference Centre for Inherited Platelet Disorders (CRPP), shared a post on LinkedIn about a recent article by Holly R. Foster et al, published in Hematologica Early View, adding:
“Foster HR, Herbert N, Di Buduo CA, …Ghevaert C. Thyroid hormones induce an acute platelet release mechanism via integrin αVβ3. Haematologica.
This fascinating study led by Cedric Ghevaert in Cambridge, shows how thyroid hormones potentially modulate platelet production by megakaryocytes (MKs) in response to a sudden and acute platelet loss.
It is cleverly put together combining studies on plateletpheresis donors, a mouse model of acute platelet depletion, and flow dependent platelet production using cord blood derived MKs and silk-based bioreactor technology.
A striking finding was that thyroid hormone (or its analogs) used αvβ3 integrin-mediated signaling in mature MKs to stimulate proplatelet formation.
This was based on the use of a specific inhibitor, tetrac, itself susceptible to enter the cell.
The older literature tells us that αvβ3 is indeed in MKs but its presence decreases with maturation.
Significantly, αvβ3 is absent from many patients with Glanzmann thrombasthenia (GT) due to ITGB3 gene defects but is increased in platelets from patients with ITGA2B gene defects and a more selective deletion of αIIbβ3.
Interesting to ask therefore how the above study would translate clinically to patients with Glanzmann thrombasthenia?”
Title: Thyroid hormones induce an acute platelet release mechanism via integrin αVβ3
Authors: Holly R. Foster, Nina Herbert, Christian A. Di Buduo, Anna P. Schmidt, Juan Fang, Ratnashree Biswas, Momal Taimoor, Amie K. Waller, Daniel Howard, Thomas M. Vallance, Moyra Lawrence, Annett Mueller, Thomas Moreau, Amanda L. Evans, Ernest Turro, Roman Fischer, David A. Wilcox, Karin M. Hoffmeister, Alessandra Balduini, Cedric Ghevaert
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