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MicroRNA-211-5p attenuates spinal cord injury via targeting of activating transcription factor 6
Haocong Zhang1, Meihui Piao1, Mingming Guo1
1Department of Orthopaedics, The General Hospital of Northern Theater Command, Shenyang, Liaoning, 110016, China.
Abstract:
The recovery of spinal cord injury (SCI) involves multiple factors, of which miRNAs take an important part. In this study, we evaluated the function of microRNA-211-5p (miR-211-5p) on SCI in a rat model. SCI model was established using modified Allen's weight-drop method and Basso-Bcattie-Bresnahan score was applied to assess the locomotor function. MiR-211-5p agomir was utilized to increase miR-211-5p expression and endoplasmic reticulum (ER) stress inhibitor, 4-PBA (4-phenylbutyric acid), was utilized to suppress ER stress. Neuron apoptosis and the expressions of miR-211-5p, activating transcription factor 6 (ATF6), apoptosis-related proteins, pro-inflammatory cytokines and endoplasmic reticulum stress-related proteins were detected. Dual luciferase reporter gene assay was performed to verify the binding between miR-211-5p and ATF6. The results showed that miR-211-5p directly targeted ATF6. MiR-211-5p was down-regulated and ATF6 was up-regulated in SCI rats. Both interferences with miR-211-5p agomir and 4-PBA effectively attenuated neuron apoptosis and reversed the expressions of apoptosis, inflammation and endoplasmic reticulum stress-related molecules post SCI in rats. These findings demonstrated that miR-211-5p could effectively alleviate SCI-induced neuron apoptosis and inflammation via directly targeting ATF-6 and regulating ER stress.
Insights
MicroRNA-211-5p (miR-211-5p) alleviates spinal cord injury (SCI) by targeting ATF6. Upregulating miR-211-5p reduces neuron apoptosis and inflammation, offering a potential therapeutic strategy for SCI recovery.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Spinal cord injury (SCI) recovery is complex, with microRNAs (miRNAs) playing a significant role.
- Understanding the specific functions of miRNAs in SCI pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of microRNA-211-5p (miR-211-5p) in a rat model of spinal cord injury (SCI).
- To determine if miR-211-5p targets activating transcription factor 6 (ATF6) and influences endoplasmic reticulum (ER) stress pathways.
Main Methods:
- An SCI rat model was established using the modified Allen's weight-drop method.
- Locomotor function was assessed using the Basso-Beattie-Bresnahan score.
- miR-211-5p expression was modulated using an agomir, and ER stress was inhibited with 4-phenylbutyric acid (4-PBA).
- Neuron apoptosis, protein expression (including ATF6, apoptosis-related, pro-inflammatory, and ER stress markers), and miR-211-5p levels were analyzed.
- A dual luciferase reporter gene assay confirmed the direct interaction between miR-211-5p and ATF6.
Main Results:
- miR-211-5p was found to directly target ATF6.
- In SCI rats, miR-211-5p expression was decreased, while ATF6 expression was increased.
- Administration of miR-211-5p agomir and 4-PBA significantly reduced neuron apoptosis post-SCI.
- Both interventions reversed the expression of molecules associated with apoptosis, inflammation, and ER stress in SCI rats.
Conclusions:
- miR-211-5p plays a protective role in SCI by directly targeting ATF6.
- Upregulation of miR-211-5p effectively mitigates SCI-induced neuron apoptosis and inflammation.
- Targeting miR-211-5p and regulating ER stress presents a promising therapeutic avenue for spinal cord injury.
- These findings highlight the therapeutic potential of miR-211-5p in SCI recovery.
