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Published on: April 12, 2021
Platelet CLEC-2 and lung development
Katsue Suzuki-Inoue1, Nagaharu Tsukiji1
1Department of Clinical and Laboratory Medicine Faculty of Medicine University of Yamanashi Chuo Japan.
Insights
Platelets actively influence embryonic development by releasing growth factors that are crucial for lung formation and blood/lymphatic vessel separation. This highlights platelets
Area of Science:
- Developmental Biology
- Hematology
- Cell Biology
Background:
- Blood cells, particularly platelets, are increasingly recognized for their active roles beyond transport during embryonic development.
- Platelet CLEC-2 (C-type lectin-like receptor 2) interacts with podoplanin (PDPN) on lymphatic endothelial cells (LECs).
- This interaction is critical for proper lung development and vascular system separation.
Purpose of the Study:
- To review the role of platelet CLEC-2 in embryonic lung development and vascular morphogenesis.
- To elucidate the mechanism by which platelets influence cell differentiation and tissue formation.
- To highlight the function of platelet-derived transforming growth factor-beta (TGF-β) in developmental processes.
Main Methods:
- Review of the State of the Art lecture presented at the ISTH congress 2019.
- Analysis of findings from mouse models with deleted platelet CLEC-2.
- Examination of receptor-ligand interactions (CLEC-2/PDPN) and downstream signaling (TGF-β).
Main Results:
- Deletion of platelet CLEC-2 in mice leads to lung malformation and impaired blood/lymphatic vessel separation, resulting in perinatal death.
- Platelet activation via CLEC-2/PDPN binding on LECs releases TGF-β, inhibiting LEC migration and promoting vascular separation.
- TGF-β also drives lung mesothelial cell differentiation into myofibroblasts, essential for lung elasticity and inflation.
Conclusions:
- Platelets are essential regulators of embryonic lung development, acting as a natural drug delivery system.
- The CLEC-2/PDPN interaction is a key pathway for platelet-mediated TGF-β release during development.
- This mechanism ensures proper lung structure and vascular network formation, critical for postnatal survival.
Abstract:
In this article, the State of the Art lecture "Platelet CLEC-2 and Lung Development" presented at the ISTH congress 2019 is reviewed. During embryonic development, blood cells are often considered as porters of nutrition and oxygen but not as active influencers of cell differentiation. However, recent studies revealed that platelets actively facilitate cell differentiation by releasing biological substances during development. C-type lectin-like receptor 2 (CLEC-2) has been identified as a receptor for the platelet-activating snake venom rhodocytin. An endogenous ligand of CLEC-2 is the membrane protein podoplanin (PDPN), which is expressed on the surface of certain types of tumor cells and lymphatic endothelial cells (LECs). Deletion of CLEC-2 from platelets in mice results in death just after birth due to lung malformation and blood/lymphatic vessel separation. During development, lymphatic vessels are derived from cardinal veins. At this stage, platelets are activated by binding of CLEC-2 to LEC PDPN and release trandforming growth factor-β (TGF-β). This cytokine inhibits LEC migration and proliferation, facilitating blood/lymphatic vessel separation. TGF-β released upon platelet-expressed CLEC-2/LEC PDPN also facilitates differentiation of lung mesothelial cells into alveolar duct myofibroblasts (adMYFs) in the developing lung. AdMYFs generate elastic fibers inside the lung, so that the lung can be properly inflated. Thus, platelets act as an ultimate natural drug delivery system that enables biological substances to be specifically delivered to the target at high concentrations by receptor/ligand interactions during development.
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