NR3C1 overexpression regulates the expression and alternative splicing of inflammation-associated genes involved in PTSD.

Linfeng Li, Wenlong Xing, Liang Jiang, Dong Chen, Guiqing Zhang

Gene 2023 Apr 05

filter terms:

NR3C1-encoding glucocorticoid receptors have dual roles as RNA-binding protein and transcription factor. Recent studies revealed that NR3C1 might play an important role in the pathogenesis of PTSD (Post-traumatic stress disorder). However, its molecular mechanism remained unclear. In the present study, a neuronal cell model was constructed by transfecting a NR3C1-overexpressing plasmid pIRES-hrGFP-1a-NR3C1 or empty vector into HT22 cells. The changes in global transcription levels and alternative splicing events in HT22 cells after NR3C1 overexpression were analyzed by RNA sequencing. Compared with the empty vector control, the expression of inflammatory factors were differentially regulated by NR3C1, including genes involved in chemokine signal pathway, PI3K-Akt signal pathway, cytokine receptor interaction, neural ligand-receptor interaction and so on. In addition, NR3C1 regulated the alternative splicing of many genes involved in immune response, axon formation, stress response and inflammation. This study was the first to perform a transcriptome analysis of differential gene expression and alternative splicing in a NR3C1-overexpressing HT22 cell model. Our results suggested that NR3C1 could manipulate the expression of inflammatory transcription factors and their alternative splicing patterns, subsequently affecting the expression of downstream targets, may be leading to the onset of PTSD. This study will provide new insights in the NR3C1-mediated gene regulation in relation to PTSD. Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

Citation

Linfeng Li, Wenlong Xing, Liang Jiang, Dong Chen, Guiqing Zhang. NR3C1 overexpression regulates the expression and alternative splicing of inflammation-associated genes involved in PTSD. Gene. 2023 Apr 05;859:147199