Chi3l3 induces oligodendrogenesis in an experimental model of autoimmune neuroinflammation
| Autor: | Starossom, Sarah C., Campo Garcia, Juliana, Woelfle, Tim, Romero-Suarez, Silvina, Olah, Marta, Watanabe, Fumihiro, Cao, Li, Yeste, Ada, Tukker, John J., Quintana, Francisco J., Imitola, Jaime, Witzel, Franziska, Schmitz, Dietmar, Morkel, Markus, Paul, Friedemann, Infante-Duarte, Carmen, Khoury, Samia J. |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Encephalomyelitis
Autoimmune Experimental MAP Kinase Signaling System Science animal diseases EGFR protein mouse metabolism [Neural Stem Cells] multiple sclerosis Article metabolism [Oligodendroglia] Mice chitotriosidase Neural Stem Cells oligodendrogenesis Lectins Animals Humans Chitinase-3-Like Protein 1 metabolism [beta-N-Acetylhexosaminidases] lcsh:Science metabolism [Chitinase-3-Like Protein 1] metabolism [Hexosaminidases] CHI3L1 protein human Chil3 protein mouse beta-N-Acetylhexosaminidases ErbB Receptors Oligodendroglia HEK293 Cells Hexosaminidases nervous system metabolism [Lectins] Female lcsh:Q ddc:500 etiology [Encephalomyelitis Autoimmune Experimental] Function and Dysfunction of the Nervous System metabolism [ErbB Receptors] |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019) Nature Communications 10(1), 217 (2019). doi:10.1038/s41467-018-08140-7 Nature Communications |
| DOI: | 10.1038/s41467-018-08140-7 |
| Popis: | In demyelinating diseases including multiple sclerosis (MS), neural stem cells (NSCs) can replace damaged oligodendrocytes if the local microenvironment supports the required differentiation process. Although chitinase-like proteins (CLPs) form part of this microenvironment, their function in this differentiation process is unknown. Here, we demonstrate that murine Chitinase 3-like-3 (Chi3l3/Ym1), human Chi3L1 and Chit1 induce oligodendrogenesis. In mice, Chi3l3 is highly expressed in the subventricular zone, a stem cell niche of the adult brain, and in inflammatory brain lesions during experimental autoimmune encephalomyelitis (EAE). We find that silencing Chi3l3 increases severity of EAE. We present evidence that in NSCs Chi3l3 activates the epidermal growth factor receptor (EGFR), thereby inducing Pyk2-and Erk1/2- dependent expression of a pro-oligodendrogenic transcription factor signature. Our results implicate CLP-EGFR-Pyk2-MEK-ERK as a key intrinsic pathway controlling oligodendrogenesis. Chitinase 3-like-3 (Chi3l3) is expressed in microglia, but its function is not clear. Here the authors show that Chi3l3 is expressed in the subventricular zone in mouse experimental immune encephalitis, which induces oligodendrogenesis. |
| Databáze: | OpenAIRE |
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