Extracellular Vesicles: An Emerging Mechanism Governing the Secretion and Biological Roles of Tenascin-C.

Lucas Albacete-Albacete,Miguel Sánchez-Álvarez,Miguel Angel Del Pozo

doi:10.3389/fimmu.2021.671485

Lucas Albacete-Albacete, Miguel Sánchez-Álvarez + Show 1 more

Open Access

https://doi.org/10.3389/fimmu.2021.671485

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Abstract

ECM composition and architecture are tightly regulated for tissue homeostasis. Different disorders have been associated to alterations in the levels of proteins such as collagens, fibronectin (FN) or tenascin-C (TnC). TnC emerges as a key regulator of multiple inflammatory processes, both during physiological tissue repair as well as pathological conditions ranging from tumor progression to cardiovascular disease. Importantly, our current understanding as to how TnC and other non-collagen ECM components are secreted has remained elusive. Extracellular vesicles (EVs) are small membrane-bound particles released to the extracellular space by most cell types, playing a key role in cell-cell communication. A broad range of cellular components can be transported by EVs (e.g. nucleic acids, lipids, signalling molecules and proteins). These cargoes can be transferred to target cells, potentially modulating their function. Recently, several extracellular matrix (ECM) proteins have been characterized as bona fide EV cargoes, exosomal secretion being particularly critical for TnC. EV-dependent ECM secretion might underpin diseases where ECM integrity is altered, establishing novel concepts in the field such as ECM nucleation over long distances, and highlighting novel opportunities for diagnostics and therapeutic intervention. Here, we review recent findings and standing questions on the molecular mechanisms governing EV–dependent ECM secretion and its potential relevance for disease, with a focus on TnC.

Highlights

Multicellularity drove the emergence of cell differentiation and functional specialization, changing the continuous communication cells establish with their surrounding environment
Throughout the past decade, the study of extracellular vesicles (EVs)-associated extracellular matrix (ECM) components has expanded our understanding of ECM biology
EVs have been suggested as integral components of stromal environments [172, 173], and enable the impact of ECMsecreting cell populations on distant organismal locations

Summary

INTRODUCTION

Multicellularity drove the emergence of cell differentiation and functional specialization, changing the continuous communication cells establish with their surrounding environment. Immune cell-derived EVs are involved in other inflammatory processes such as tissue fibrosis, where an increase in ECM deposition has been described to impact cell behaviour, including cell proliferation, migration and differentiation, and subsequently participating in the development of several pathologies. Caveolin-1 [Cav; a pivotal regulator of membrane organization, mechanoadaptation, ECM remodeling and cholesterol efflux [16, 203,204,205]] is strictly required for the appropriate biogenesis of exosome subpopulations of different sizes, and the sorting onto them of specific ECM components, through the control of cholesterol content in endosomal compartments This effect varies across ECM exosome cargoes, suggesting that the extent of dependency on different secretion routes may be specific for each ECM component; for example, in contrast with TnC, FN deposition is only partially decreased upon disruption of exososomal secretion. EVs origin: cell type/tissue from which EVs containing TnC were detected; WB: western blotting

Result

Findings

CONCLUDING REMARKS AND PERSPECTIVES