BRD4 inhibition attenuates inflammatory response in microglia and facilitates recovery after spinal cord injury in rats

Journal of Cellular and Molecular Medicine
Jianle WangXiaolei Zhang

Abstract

The pathophysiology of spinal cord injury (SCI) involves primary injury and secondary injury. For the irreversibility of primary injury, therapies of SCI mainly focus on secondary injury, whereas inflammation is considered to be a major target for secondary injury; however the regulation of inflammation in SCI is unclear and targeted therapies are still lacking. In this study, we found that the expression of BRD4 was correlated with pro-inflammatory cytokines after SCI in rats; in vitro study in microglia showed that BRD4 inhibition either by lentivirus or JQ1 may both suppress the MAPK and NF-κB signalling pathways, which are the two major signalling pathways involved in inflammatory response in microglia. BRD4 inhibition by JQ1 not only blocked microglial M1 polarization, but also repressed the level of pro-inflammatory cytokines in microglia in vitro and in vivo. Furthermore, BRD4 inhibition by JQ1 can improve functional recovery and structural disorder as well as reduce neuron loss in SCI rats. Overall, this study illustrates that microglial BRD4 level is increased after SCI and BRD4 inhibition is able to suppress M1 polarization and pro-inflammatory cytokine production in microglia which ultimately promotes functional reco...Continue Reading

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Citations

Dec 26, 2019·SLAS Discovery·Alexander N PhillipouPeter D Craggs
Apr 24, 2020·Circulation Research·Patricia Cristine BorckJorge Plutzky
Sep 29, 2020·Frontiers in Cellular Neuroscience·Yao LiXiangyang Wang
Jan 20, 2021·Signal Transduction and Targeted Therapy·Nian WangRui Kang
Oct 20, 2020·Osteoarthritis and Cartilage·M F Rai
Jun 19, 2021·International Journal of General Medicine·Jun RaoLi Fan
Aug 16, 2021·Ecotoxicology and Environmental Safety·Zhonggui GongZongping Liu
Aug 28, 2021·Biomolecules·Nieves Lara-Ureña, Mario García-Domínguez

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Methods Mentioned

BETA
transfection
protein assay
light microscopy
PCR
ELISA

Software Mentioned

GraphPad Prism
Image Lab

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