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Lnc RNA GAS 5 inhibits microglial M2 polarization and exacerbates demyelination
Author(s) -
Sun Dingya,
Yu Zhongwang,
Fang Xue,
Liu Mingdong,
Pu Yingyan,
Shao Qi,
Wang Dan,
Zhao Xiaolin,
Huang Aijun,
Xiang Zhenghua,
Zhao Chao,
Franklin Robin JM,
Cao Li,
He Cheng
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201643668
Subject(s) - microglia , remyelination , gas5 , multiple sclerosis , neuroinflammation , experimental autoimmune encephalomyelitis , macrophage polarization , inflammation , regulator , long non coding rna , oligodendrocyte , microbiology and biotechnology , biology , neuroscience , myelin , immunology , chemistry , downregulation and upregulation , macrophage , central nervous system , biochemistry , gene , in vitro
The regulation of inflammation is pivotal for preventing the development or reoccurrence of multiple sclerosis ( MS ). A biased ratio of high‐M1 versus low‐M2 polarized microglia is a major pathological feature of MS . Here, using microarray screening, we identify the long noncoding RNA (lnc RNA ) GAS 5 as an epigenetic regulator of microglial polarization. Gain‐ and loss‐of‐function studies reveal that GAS 5 suppresses microglial M2 polarization. Interference with GAS 5 in transplanted microglia attenuates the progression of experimental autoimmune encephalomyelitis ( EAE ) and promotes remyelination in a lysolecithin‐induced demyelination model. In agreement, higher levels of GAS 5 are found in amoeboid‐shaped microglia in MS patients. Further, functional studies demonstrate that GAS 5 suppresses transcription of TRF 4, a key factor controlling M2 macrophage polarization, by recruiting the polycomb repressive complex 2 ( PRC 2), thereby inhibiting M2 polarization. Thus, GAS 5 may be a promising target for the treatment of demyelinating diseases.