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Updated: Jan 8, 2026
A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration
Published on: February 27, 2018
Microglial RUNX1/RBM47 ablation inhibits neuronal ferroptosis via regulating the cGAS-STING-MEF2C pathway in mice
Shanshan Wang1, Zankai Wu2, Wenqin Song1
1Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China.
Abstract:
Activation of the cGAS-STING pathway has been proposed as a potential pathogenic mechanism underlying postoperative cognitive dysfuncton (POCD). Analysis of public transcriptomic data from the hippocampus of male mice suggests upregulation of Rbm47 in an experimental POCD model. In vitro, knockdown (KD) of Rbm47 in BV2 cells reduces levels of cGAS, STING, TNF-α, IL-6, and IFN-β under isoflurane and lipopolysaccharide (Iso + LPS) conditions. HT22 cells exposed to culture medium from Rbm47-KD BV2 cells treated with Iso + LPS show increased levels of MEF2C, GPX4, GSH, and SOD, and reduced levels of MDA and iron. Microglial Rbm47 overexpression amplifies cGAS-STING signaling and aggravates neuronal ferroptosis, which is reversed by the cGAS inhibitor RU.521. Rbm47 KD combined with RU.521 treatment synergistically ameliorates POCD in male mice. Mechanistically, the RRM2 domain of RBM47 interacts with the 3'UTR of cGAS mRNA, enhancing its stability. RUNX1 directly binds to the Rbm47 promoter and facilitates its transcription. RUNX1 overexpression activates the RBM47-cGAS-STING axis and exacerbates neuronal ferroptosis. Conversely, RUNX1 ablation ameliorates POCD, dampens the cGAS-STING signaling, and inhibits ferroptosis, which is abolished by RBM47 depletion. Our findings suggest that repression of RUNX1/RBM47 may represent a promising therapeutic strategy for POCD.
Insights
Repressing RUNX1 and RBM47 may offer a new treatment for postoperative cognitive dysfunction (POCD). This study reveals how RBM47 regulates the cGAS-STING pathway, impacting neuronal ferroptosis and POCD development.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Postoperative cognitive dysfunction (POCD) is linked to cGAS-STING pathway activation.
- Rbm47 is upregulated in experimental POCD models, suggesting its involvement.
Purpose of the Study:
- To investigate the role of Rbm47 in the cGAS-STING pathway and its contribution to POCD.
- To explore the therapeutic potential of targeting the RUNX1/RBM47 axis for POCD treatment.
Main Methods:
- Analysis of transcriptomic data from mouse hippocampus.
- In vitro experiments using BV2 and HT22 cell lines with Rbm47 knockdown (KD) and overexpression.
- In vivo studies involving Rbm47 KD and cGAS inhibitor (RU.521) treatment in male mice.
- Investigation of the molecular interaction between RBM47 and cGAS mRNA, and RUNX1 binding to the Rbm47 promoter.
Main Results:
- Rbm47 KD reduced cGAS-STING pathway activation and inflammatory cytokine production in vitro.
- Rbm47 KD or cGAS inhibition ameliorated POCD symptoms in mice.
- RBM47 stabilizes cGAS mRNA, and RUNX1 promotes Rbm47 transcription.
- RUNX1 overexpression exacerbated POCD and ferroptosis, while RUNX1 ablation had protective effects.
Conclusions:
- The RUNX1/RBM47 axis is a key regulator of the cGAS-STING pathway and neuronal ferroptosis in POCD.
- Targeting RUNX1/RBM47 presents a promising therapeutic strategy for preventing and treating POCD.
