Abstract
For decades, platelets have been known for their central role in hemostasis and their ability to release bioactive molecules, allowing inter-platelet communication and crosstalk with the immune system and vascular cells. However, with the detection of microRNAs in platelets and platelet-derived microvesicles (MVs), a new level of inter-cellular regulation was revealed. By shedding MVs from their plasma membrane, platelets are able to release functional microRNA complexes that are protected from plasma RNases. Upon contact with macrophages, endothelial cells and smooth muscle cells platelet microRNAs are rapidly internalized and fine-tune the functionality of the recipient cell by post-transcriptional reprogramming. Moreover, microRNA transfer by platelet MVs allows infiltration into tissues with limited cellular access such as solid tumors, thereby they not only modulate tumor progression but also provide a potential route for drug delivery. Understanding the precise mechanisms of horizontal transfer of platelet microRNAs under physiological and pathological conditions allows to design side-specific therapeutic (micro)RNA delivery systems. This review summarizes the current knowledge and the scientific evidence of horizontal microRNA transfer by platelets and platelet-derived MVs into vascular and non-vascular cells and its physiological consequences.
Highlights
Platelets are anucleate, highly abundant blood cells that constantly patrol the microvasculature to monitor vascular injuries and act as sentinels to trace inflammatory and infectious processes
A prerequisite for efficient miRNA transfer is close proximity between donor and recipient cells, which is facilitated by a broad variety of platelet surface molecules such as P-selectin, glycoprotein (GP)Ib, GPIIb/IIIa, intercellular adhesion molecule (ICAM) 2 and CD40 ligand (CD40L), which are exposed on the platelet surface upon activation
TNTs comprise of several individual tunneling nanotubes that run in parallel and are connected by N-cadherins
Summary
Highly abundant blood cells that constantly patrol the microvasculature to monitor vascular injuries and act as sentinels to trace inflammatory and infectious processes. A prerequisite for efficient miRNA transfer is close proximity between donor and recipient cells, which is facilitated by a broad variety of platelet surface molecules such as P-selectin, glycoprotein (GP)Ib, GPIIb/IIIa, intercellular adhesion molecule (ICAM) 2 and CD40 ligand (CD40L), which are exposed on the platelet surface upon activation. This pairing of miRNA transfer to platelet activation, guarantees a concerted and fineregulated – not fully deciphered – release of cellular material at specialized loci within the human body. PMVs are increased in various diseases such as cancer and immune disease and due to their small size allow the transport of genetic information into specialized microenvironments such as permeable vasculature of solid tumors
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