Matricellular proteins are secreted, nonstructural proteins that regulate the extracellular matrix (ECM) and interactions between cells through modulation of growth factor signaling, cell adhesion, migration, and proliferation. Despite being well described in the context of nonneuronal tissues, recent studies have revealed that these molecules may also play instrumental roles in central nervous system (CNS) development and diseases. In this minireview, we discuss the matricellular protein families SPARC (secreted protein acidic and rich in cysteine), Hevin/SC1 (SPARC-like 1), TN-C (Tenascin C), TSP (Thrombospondin), and CCN (CYR61/CTGF/NOV), which are secreted by astrocytes during development. These proteins exhibit a reduced expression in adult CNS but are upregulated in reactive astrocytes following injury or disease, where they are well placed to modulate the repair processes such as tissue remodeling, axon regeneration, glial scar formation, angiogenesis, and rewiring of neural circuitry. Conversely, their reexpression in reactive astrocytes may also lead to detrimental effects and promote the progression of neurodegenerative diseases. 1. Introduction Astrocytes secrete numerous factors and active molecules [1–4], which modulate synapse development, neuronal activity, and plasticity during development and in the mature brain [5–10]. In particular, immature astrocytes produce and secrete many types of proteins that allow them to remodel the extracellular matrix (ECM) surrounding neurons and synapses [11]. In addition, astrocytes have the ability to react to any kind of insult or change in their environment, physical, viral, or chronic disease, and work side by side with microglia, the immune cells of the brain, in order to contain and to repair the brain from injuries [12, 13]. Astrocyte reactivity is associated with striking changes in gene expression and morphology [14, 15]. It has been demonstrated that reactive astrocytes revert to a partially immature molecular profile [16], which allow them to reexpress a variety of factors/proteins required for tissue remodelling around injury sites [13]. Some of these proteins have direct roles on modulation of ECM and cell to cell interactions. One mechanism used by reactive astrocytes to reshape their microenvironment is through the secretion of matricellular proteins. Matricellular proteins are a family of structurally unrelated proteins that are secreted into the extracellular space. They act as nonstructural regulators of the ECM and cell-matrix interactions through modulation of growth factor signaling,
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