Open AccessGenome-Wide Screen and Validation of Microglia Pro-Inflammatory Mediators in Stroke
Author(s) -
Jing Wu,
Zhuoze Wu,
Ao-Di He,
Tongmei Zhang,
Ping Zhang,
Jing Jin,
Sisi Li,
Gaigai Li,
Xinyan Li,
Shiqi Liang,
Lei Pei,
Rong Liu,
Qing Tian,
Ximiao He,
Youming Lu,
Zhouping Tang,
Hao Li
Publication year - 2021
Publication title -
aging and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.808
H-Index - 54
ISSN - 2152-5250
DOI - 10.14336/ad.2020.0926
Subject(s) - microglia , medicine , stroke (engine) , genome , computational biology , inflammation , bioinformatics , immunology , gene , genetics , biology , mechanical engineering , engineering
Stroke activates microglia pro-inflammatory response that not only induces the early neuronal injuries but also causes the secondary brain infarction. Yet, the underlying mechanisms for how microglia become activated in stroke are still unknown. Here, using the next-generation of RNA sequencing we find a total of 778 genes increasingly expressed in brain of stroke mice. Of these, we identified Hmgb2 as a microglia pro-inflammatory mediator by promoting the transcription of Ctss. Inhibition of either Hmgb2 or Ctss blocks microglia pro-inflammatory response and protects against brain damages and improves the neurological functions of stroke mice. This study uncovers Hmgb2 and Ctss as the major microglia inflammatory response mediators in stroke and hence warrants the promising targets for stroke therapies.