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High‐mobility group box 1 from reactive astrocytes enhances the accumulation of endothelial progenitor cells in damaged white matter
Author(s) -
Hayakawa Kazuhide,
Miyamoto Nobukazu,
Seo Ji Hae,
Pham LocDuyen D.,
Kim KyuWon,
Lo Eng H.,
Arai Ken
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12120
Subject(s) - hmgb1 , rage (emotion) , astrocyte , white matter , progenitor cell , microbiology and biotechnology , biology , immunology , medicine , endocrinology , stem cell , neuroscience , inflammation , central nervous system , radiology , magnetic resonance imaging
High‐mobility group box 1 ( HMGB 1) was initially described as a damage‐associated‐molecular‐pattern ( DAMP ) mediator that worsens acute brain injury after stroke. But, recent findings suggest that HMGB 1 can play a surprisingly beneficial role during stroke recovery by promoting endothelial progenitor cell ( EPC ) function and vascular remodeling in cortical gray matter. Here, we ask whether HMGB 1 may also influence EPC responses in white matter injury. The standard lysophosphatidylcholine ( LPC ) injection model was used to induce focal demyelination in the corpus callosum of mice. Immunostaining showed that within the focal white matter lesions, HMGB 1 was up‐regulated in GFAP ‐positive reactive astrocytes, along with the accumulation of Flk1/ CD 34‐double‐positive EPC s that expressed pro‐recovery mediators such as brain‐derived neurotrophic factor and basic fibroblast growth factor. Astrocyte– EPC signaling required the HMGB 1 receptor RAGE as treatment with RAGE ‐neutralizing antibody significantly decreased EPC accumulation. Moreover, suppression of HMGB 1 with si RNA in vivo significantly decreased EPC numbers in damaged white matter as well as proliferated endothelial cell numbers. Finally, in vitro cell culture systems confirmed that HMGB 1 directly affected EPC function such as migration and tube formation. Taken together, our findings suggest that HMGB 1 from reactive astrocytes may attract EPC s to promote recovery after white matter injury.