Document Type

Journal Article

Publication Date

11-24-2015

Journal

Cell Reports

DOI

10.1016/j.celrep.2015.11.002

Keywords

Astrocytes--\metabolism; Demyelinating Diseases--metabolism; Neural Stem Cells--metabolism; Receptor, Endothelin B--metabolism

Abstract

Reactive astrogliosis is an essential and ubiquitous response to CNS injury, but in some cases, aberrant activation of astrocytes and their release of inhibitory signaling molecules can impair endogenous neural repair processes. Our lab previously identified a secreted intercellular signaling molecule, called endothelin-1 (ET-1), which is expressed at high levels by reactive astrocytes in multiple sclerosis (MS) lesions and limits repair by delaying oligodendrocyte progenitor cell (OPC) maturation. However, as ET receptors are widely expressed on neural cells, the cell- and receptor-specific mechanisms of OPC inhibition by ET-1 action remain undefined. Using pharmacological approaches and cell-specific endothelin receptor (EDNR) ablation, we show that ET-1 acts selectively through EDNRB on astrocytes-and not OPCs-to indirectly inhibit remyelination. These results demonstrate that targeting specific pathways in reactive astrocytes represents a promising therapeutic target in diseases with extensive reactive astrogliosis, including MS.

Comments

Reproduced with permission of Elsevier B.V. Cell Reports.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Peer Reviewed

1

Open Access

1

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