Abstract
Increasing evidence suggests the potential role of extracellular vesicles (EVs) in many lung diseases. According to their subcellular origin, secretion mechanism, and size, EVs are currently classified into three subpopulations: exosomes, microvesicles, and apoptotic bodies. Exosomes are released in most biofluids, including airway fluids, and play a key role in intercellular communication via the delivery of their cargo (e.g., microRNAs (miRNAs)) to target cell. In a physiological context, lung exosomes present protective effects against stress signals which allow them to participate in the maintenance of lung homeostasis. The presence of air pollution alters the composition of lung exosomes (dysregulation of exosomal miRNAs) and their homeostatic property. Indeed, besides their potential as diagnostic biomarkers for lung diseases, lung exosomes are functional units capable of dysregulating numerous pathophysiological processes (including inflammation or fibrosis), resulting in the promotion of lung disease progression. Here, we review recent studies on the known and potential role of lung exosomes/exosomal miRNAs, in the maintaining of lung homeostasis on one hand, and in promoting lung disease progression on the other. We will also discuss using exosomes as prognostic/diagnostic biomarkers as well as therapeutic tools for lung diseases.
Highlights
Lung diseases are among the leading causes of death worldwide
Cells can release three main types of extracellular vesicles (EVs) classified according to their sub-cellular origin, secretion mechanism, and size (Table 1): exosomes (30–150 nm), which are internal vesicles generated within late endosomes/multivesicular bodies (MVBs) and released to an extracellular environment after fusion of MVBs with the plasma membrane [10,11,12]; microvesicles (MVs) are larger in size, 100 nm to 1 μm, and are formed by the outward budding and scission of plasma membrane [13]; and apoptotic bodies (ABs), the largest subtype of EVs (1–5 μm), which are released from plasma membrane of apoptotic cells [14,15]
It is important to mention that the interpretation of biological function of individual altered miRNAs is difficult because miRNAs work together and generally have small individual effects upon gene expression
Summary
Lung diseases are among the leading causes of death worldwide. Recently, the forum of international respiratory societies (FIRS) has reported the global burden of lung diseases [1]. Chronic obstructive pulmonary disease (COPD) affects 65 million people in the world, and about 3 million people die from it each year, making it the third leading cause of death worldwide [2,3]. The inhalation of smoke and unhealthy air (air pollution, allergens, and microbial pathogens) induces airway injury, which is a major risk factor in the development of lung diseases. Repeated exposure of lung epithelium to gaseous pollution induces chronic airway inflammation and aberrant repair processes of lung, resulting in the development of lung diseases [7,8], such as interstitial lung diseases, COPD, or asthma. We aim to summarize current knowledge about the role of EVs, principally exosomes and exosomal microRNAs (miRNAs), in lung physiology and disease pathogenesis, including COPD, asthma, acute lung injury/acute respiratory distress syndrome (ALI/ARDS), and idiopathic pulmonary fibrosis (IPF). We discuss the clinical development of exosome-based diagnosis and therapies for lung diseases
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