Extracellular Vesicles and Their Emerging Roles as Cellular Messengers in Endocrinology: An Endocrine Society Scientific Statement

Abstract

During the last decade, there has been great interest in elucidating the biological role of extracellular vesicles (EVs), particularly, their hormone-like role in cell-to-cell communication. The field of endocrinology is uniquely placed to provide insight into the functions of EVs, which are secreted from all cells into biological fluids and carry endocrine signals to engage in paracellular and distal interactions. EVs are a heterogeneous population of membrane-bound vesicles of varying size, content, and bioactivity. EVs are specifically packaged with signaling molecules, including lipids, proteins, and nucleic acids, and are released via exocytosis into biofluid compartments. EVs regulate the activity of both proximal and distal target cells, including translational activity, metabolism, growth, and development. As such, EVs signaling represents an integral pathway mediating intercellular communication. Moreover, as the content of EVs is cell-type specific, it is a "fingerprint" of the releasing cell and its metabolic status. Recently, changes in the profile of EV and bioactivity have been described in several endocrine-related conditions including diabetes, obesity, cardiovascular diseases, and cancer. The goal of this statement is to highlight relevant aspects of EV research and their potential role in the field of endocrinology.

Keywords: apoptotic body; biogenesis; cellular messenger; ectosome; exosome; extracellular vesicle; microvesicle; migrasome; oncosome; signaling.

Figure 1.

Extracellular vesicle (EV) heterogeneity. EVs can be categorized according to their size as small and large EVs. Small EV including exosomes and ectosomes and large EV including ectosomes (some EV overlap with exosomes), migrasome, apoptotic bodies, and large oncosomes. Recently, arrestin domain-containing protein 1 (ARRDC1)-mediated microvesicles (ARMMs) have been identified.

Figure 2.

Illustration of analytical workflow to analyze phosphorylated and glycosylated proteins in plasma EVs.

Figure 3.

Extracellular vesicle uptake and interaction with target cells. Adapted with permission from Moller A and Lobb RJ. Nat Rev Cancer, 2021; 20(12) © Springer Nature Limited.

Figure 4.

Extracellular vesicles (EVs; eg, small EVs such as exosomes) harvested from adipose tissue macrophages (ATMs) in obese mice promote insulin resistance while exosomes preparations from ATMs in lean mice induce insulin sensitivity and might be involved in fetal growth in gestational diabetes mellitus.

Figure 5.

The contribution of extracellular vesicles (EVs) to the pathogenesis of type 1 diabetes. Islet β cells, especially upon inflammatory stimuli, can produce EVs to activate antigen-presenting cells and T and B lymphocytes, causing insulitis and β-cell destruction. In addition to direct immune attack, T cells can also release EVs to induce β-cell apoptosis, thereby aggravating the development of type 1 diabetes.

Figure 6.

Functional role of extracellular vesicles (EVs) in essential hypertension. Adapted with permission from La Salvia S et al. Curr Hypertens Rep, 2020; 22(10) © Springer Science Business Media, LLC, part of Springer Nature.