Extracellular vesicles: emerging roles, biomarkers and therapeutic strategies in fibrotic diseases

Abstract

Extracellular vesicles (EVs), a cluster of cell-secreted lipid bilayer nanoscale particles, universally exist in body fluids, as well as cell and tissue culture supernatants. Over the past years, increasing attention have been paid to the important role of EVs as effective intercellular communicators in fibrotic diseases. Notably, EV cargos, including proteins, lipids, nucleic acids, and metabolites, are reported to be disease-specific and can even contribute to fibrosis pathology. Thus, EVs are considered as effective biomarkers for disease diagnosis and prognosis. Emerging evidence shows that EVs derived from stem/progenitor cells have great prospects for cell-free therapy in various preclinical models of fibrotic diseases and engineered EVs can improve the targeting and effectiveness of their treatment. In this review, we will focus on the biological functions and mechanisms of EVs in the fibrotic diseases, as well as their potential as novel biomarkers and therapeutic strategies.

Extracellular Vesicles as Delivery Vehicles for Non-Coding RNAs: Potential Biomarkers for Chronic Liver Diseases

“…In Mdr2-/-mice, H19 lncRNA in serum exosomes gradually increased with disease progression, indicating that this biomolecule can develop into an RNA biomarker for cholestatic injury and its progression into more severe disease. Moreover, in biliary cholangitis and biliary atresia patients, the serum level of EV-carried H19 was found to correlate with the severity of fibrotic liver injury [ 136 ].…”

“…Regarding lncRNAs, in subjects with biliary cholangitis and biliary atresia, there is a reported correlation between the severity of fibrotic liver injury and the level of EV-carried lncRNA H19 in the serum [ 136 ]. The DNA methyltransferase 1 (DNMT1)-mediated epigenetic silencing of lncRNA H19 is associated with the activation of hepatic stellate cells, which is involved in liver fibrosis [ 147 ].…”

An emerging view on vascular fibrosis molecular mediators and relevant disorders: from bench to bed

“…For example, macrophage derived EVs carrying with lncRNA GAS5 can lead to EC apoptosis, in response to excessive lipoproteins accumulation ( 75 ). Through targeting miR-138-5p/RhoC axis, EVs from macrophages show pro-fibrotic effect by transmitting circUbe3 ( 76 ). Furthermore, activated CD4 + T cells secretes EVs loading miR-142-3p, to contribute to fibrotic remodeling after myocardial infraction, via activation of myofibroblasts ( 77 ).…”

Fluorescence Tracking of Small Extracellular Vesicles In Vivo

“…When first separated from ovine red blood cells in the 1970s, sEVs were considered to be plasma membrane-enclosed organelles of uniform size (50 nm) as a group of natural products from maturing reticulocytes [ 2 ]. Mounting evidence revealed that sEVs (e.g., exosomes) are subcellular vehicles with a size range of 30–200 nm, functioning as intercellular communicators and containing a variety of biomolecule cargoes, such as proteins, nucleic acids, and carbohydrates [ 1 , 3 ]. While inheriting main biological characteristics from parental cells, sEVs play an indispensable role in many physiological and pathological conditions, where their surface proteins may represent diagnostic biomarkers in various diseases and can be found in various body fluids (e.g., urine, blood) and tissues [ 4 ].…”