Open AccessRNA i‐mediated ephrin‐B2 silencing attenuates astroglial‐fibrotic scar formation and improves spinal cord axon growth
Author(s) -
Li Yi,
Chen Ying,
Tan Ling,
Pan JingYing,
Lin WeiWei,
Wu Jian,
Hu Wen,
Chen Xue,
Wang XiaoDong
Publication year - 2017
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12723
Subject(s) - glial scar , versican , axon , ephrin , astrocyte , spinal cord , aggrecan , regeneration (biology) , spinal cord injury , central nervous system , medicine , microbiology and biotechnology , pathology , neuroscience , anatomy , biology , signal transduction , proteoglycan , cartilage , osteoarthritis , articular cartilage , alternative medicine
Summary Aims Astroglial‐fibrotic scar formation following central nervous system injury can help repair blood‐brain barrier and seal the lesion, whereas it also represents a strong barrier for axonal regeneration. Intensive preclinical efforts have been made to eliminate/reduce the inhibitory part and, in the meantime, preserve the beneficial role of astroglial‐fibrotic scar. Methods In this study, we established an in vitro system, in which coculture of astrocytes and meningeal fibroblasts was treated with exogenous transforming growth factor‐β1 ( TGF ‐β1) to form astroglial‐fibrotic scar‐like cell clusters, and thereby evaluated the efficacy of RNA i targeting ephrin‐B2 in preventing scar formation from the very beginning. We further tested the effect of RNA i‐based mitigation of astroglial‐fibrotic scar on spinal axon outgrowth on a custom‐made microfluidic platform. Results We found that si RNA targeting ephrin‐B2 significantly reduced both the number and the diameter of cell clusters induced by TGF ‐β1 and diminished the expression of aggrecan and versican in the coculture, and allowed for significantly longer extension of outgrowing spinal cord axons into astroglial‐fibrotic scar as assessed on the microfluidic platform. Conclusions These results suggest that astroglial‐fibrotic scar formation and particularly the expression of aggrecan and versican could be mitigated by ephrin‐B2 specific si RNA , thus improving the microenvironment for spinal axon regeneration.