Caveolin-1 regulates extracellular vesicle-miRNA packaging

vesicles (EVs) play an essential role in intercellular cross-talk and regulate the pathogenesis of various human diseases [1, 2]. EVs are nano-sized vesicles surrounded by lipid bilayers and are generated from almost all cell types [1]. EVs facilitate intercellular communications via surface molecule-triggered signaling or by transferring EV cargo, such as proteins and RNAs, into recipient cells [1, 2]. Recently, efforts have focused on studying EVcontaining microRNAs (EV-miRNAs) which demonstrate the ability to carry out numerous biological functions [3]. Secretion of EVs from “parent” cells facilitates a rapid removal of intracellular miRNAs via EV packaging and release. For example, in response to gram-negative bacterial infection or LPS stimulation, macrophages actively secrete selected miRNAs, such as miR-223/142, via EV-mediated manner [4]. In quiescent macrophages, miR-223/142 inhibits NLRP3 inflammasome activation. Upon exposure to G-bacteria or LPS, miR-223/142 is uridylated and encapsulated into EVs, subsequently being released from macrophages. Due to removal of miR-223/142-mediated inhibition, macrophages are activated towards M1 polarization. This activation is reflected by enhanced phagocytosis/ bacterial clearance, NO/ROS generation, and secretion of inflammatory cytokines. EV-miRNAs potentially serve as signal transmitters among cells and facilitate cell-cell cross talk. Reports have shown that EV-cargo miRNAs can be taken up by targeted recipient cells and subsequently modulate the recipients’ intracellular events [3]. For example, lung epithelial cell-derived EV-miRNAs are taken up by lung macrophages after non-infectious stimuli. A proinflammatory miRNA repertoire has been identified in EVs released by epithelial cells [2, 5]. After uptake by recipient macrophages, the intracellular levels of this miRNA repertoire is elevated and likely plays a role in modulating the activation of these macrophages [2, 5]. Exogenous EV-cargo miRNAs likely provides an immediate way to increase intracellular levels of specific miRNA repertoires. Despite these findings, many questions remain unanswered. For instance, the quantity of EVs and EV-miRNAs that are required to be taken up by the recipient cells in order to have biological effects remains unknown. More importantly, Editorial