Tao, Y.* ; Zhang, Y.* ; Jin, W.* ; Hua, N.* ; Liu, H.* ; Qi, R.* ; Huang, Z.* ; Sun, Y.* ; Jiang, D. ; Snutch, T.P.* ; Jiang, X.* ; Tao, J.*
     
 
    
        
Epigenetic regulation of beta-endorphin synthesis in hypothalamic arcuate nucleus neurons modulates neuropathic pain in a rodent pain model.
    
    
        
    
    
        
        Nat. Commun. 14:7234 (2023)
    
    
    
		
		
			
				Although beta-endorphinergic neurons in the hypothalamic arcuate nucleus (ARC) synthesize beta-endorphin (β-EP) to alleviate nociceptive behaviors, the underlying regulatory mechanisms remain unknown. Here, we elucidated an epigenetic pathway driven by microRNA regulation of β-EP synthesis in ARC neurons to control neuropathic pain. In pain-injured rats miR-203a-3p was the most highly upregulated miRNA in the ARC. A similar increase was identified in the cerebrospinal fluid of trigeminal neuralgia patients. Mechanistically, we found histone deacetylase 9 was downregulated following nerve injury, which decreased deacetylation of histone H3 lysine-18, facilitating the binding of NR4A2 transcription factor to the miR-203a-3p gene promoter, thereby upregulating miR-203a-3p expression. Further, increased miR-203a-3p was found to maintain neuropathic pain by targeting proprotein convertase 1, an endopeptidase necessary for the cleavage of proopiomelanocortin, the precursor of β-EP. The identified mechanism may provide an avenue for the development of new therapeutic targets for neuropathic pain treatment.
			
			
				
			
		 
		
			
				
					
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        Publikationstyp
        Artikel: Journalartikel
    
 
    
        Dokumenttyp
        Wissenschaftlicher Artikel
    
 
    
        Typ der Hochschulschrift
        
    
 
    
        Herausgeber
        
    
    
        Schlagwörter
        Rat Model; Histone Acetylation; Trigeminal Ganglion; Expression; Accumbens; Chromatin; System; Stress; Hypersensitivity; Involvement
    
 
    
        Keywords plus
        
    
 
    
    
        Sprache
        englisch
    
 
    
        Veröffentlichungsjahr
        2023
    
 
    
        Prepublished im Jahr 
        0
    
 
    
        HGF-Berichtsjahr
        2023
    
 
    
    
        ISSN (print) / ISBN
        2041-1723
    
 
    
        e-ISSN
        2041-1723
    
 
    
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	    Band: 14,  
	    Heft: 1,  
	    Seiten: ,  
	    Artikelnummer: 7234 
	    Supplement: ,  
	
    
 
  
        
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            Verlag
            Nature Publishing Group
        
 
        
            Verlagsort
            London
        
 
	
        
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            0000-00-00
        
 
        
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        Begutachtungsstatus
        Peer reviewed
    
 
    
        Institut(e)
        Institute of Regenerative Biology and Medicine (IRBM)
    
 
    
        POF Topic(s)
        30202 - Environmental Health
    
 
    
        Forschungsfeld(er)
        Lung Research
    
 
    
        PSP-Element(e)
        G-509400-001
    
 
    
        Förderungen
        MOE Key Laboratory of Geriatric Diseases and Immunology - Priority Academic Program Development of Jiangsu Higher Education Institutions
Practice Innovation Program of Jiangsu Province
Postgraduate Research amp
Project of State Key Laboratory of Radiation Medicine and Protection
Jiangsu Key Laboratory of Neuropsychiatric Diseases
Science and Technology Bureau of Suzhou
Natural Science Foundation of Jiangsu Province
National Natural Science Foundation of China
This study was supported by the National Natural Science Foundation of China (82371218, 82271245, and 82071236), the Natural Science Foundation of Jiangsu Province (BK20211073), the Science and Technology Bureau of Suzhou (SYS2020129), the Jiangsu Key Lab
    
 
    
        Copyright
        
    
 	
    
    
    
    
    
        Erfassungsdatum
        2023-11-28