|
Status |
Public on Mar 28, 2022 |
Title |
Transcriptome analysis of LPS-stimulated BMDMs pretreated with Ctrl MO or Regnase-1-targeting MOs (Reg1-MOs) |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
Regnase-1 plays essential roles in restricting inflammation by acting as a RNase degrading mRNAs involved in immune reactions via the recognition of stem-loop structures in the 3’untranslated regions (UTRs). Dysregulated expression of Regnase-1 is implicated in the pathogenesis of inflammatory and autoimmune diseases in mice and humans. Here we developed a novel therapeutic strategy to suppress inflammatory responses by blocking Regnase-1 self-regulation, which was enabled by the simultaneous use of two antisense phosphorodiamidate morpholino oligonucleotides (MOs) to alter the binding affinity of Regnase-1 towards the stem-loop structures present in its 3’UTR. The Regnase-1-targeting MOs successfully stabilized Regnase-1 mRNA expression. Furthermore, increasing the abundance of Regnase-1 by MO treatment effectively reduced multiple pro-inflammatory transcripts that were controlled by Regnase-1 in BMDMs. Collectively, these data suggested that MO-mediated disruption of the Regnase-1 self-regulation pathway is an attractive therapeutic strategy to enhance Regnase-1 abundance, which could provide clinical benefits for treating inflammatory diseases through the suppression of inflammation.
|
|
|
Overall design |
Bome marrow cells were isolated from wild-type B6 animals, and were cultured in macrophage growth medium for 7 days (exchange with fresh macrophage growth medium on D4). BMDMs were transfected with Ctrl MO (2 µM) or Reg1-MOs (2 µM) together with Endoporter for 24 hours, followed by stimulation with LPS for 4 hours.
|
|
|
Contributor(s) |
Tse K, Yoshinaga M, Hia F, Takeuchi O |
Citation(s) |
35544597 |
|
Submission date |
Aug 24, 2021 |
Last update date |
Jul 10, 2022 |
Contact name |
Ka Man Carman Tse |
E-mail(s) |
isabeltse711@gmail.com
|
Phone |
075-753-9500
|
Organization name |
Kyoto University
|
Department |
Graduate School of Medicine, Department of Medical Chemistry
|
Lab |
Takeuchi lab
|
Street address |
Yoshidakonoecho, Sakyo-ku
|
City |
Kyoto |
State/province |
Kyoto |
ZIP/Postal code |
606-8501 |
Country |
Japan |
|
|
Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
Samples (4)
|
|
Relations |
BioProject |
PRJNA757257 |
SRA |
SRP333858 |