Author:
Shi Yunhong,Liu Yidan,Wu Caiqing,Liu Xiuxing,Hu Wenfei,Yang Zhenlan,Li Zhidong,Li Yangyang,Deng Caibin,Wei Kun,Gu Chenyang,Chen Xuhao,Su Wenru,Zhuo Yehong
Abstract
Abstract
Background
Retinal ischemia–reperfusion (RIR) injury refers to an obstruction in the retinal blood supply followed by reperfusion. Although the molecular mechanism underlying the ischemic pathological cascade is not fully understood, neuroinflammation plays a crucial part in the mortality of retinal ganglion cells.
Methods
Single-cell RNA sequencing (scRNA-seq), molecular docking, and transfection assay were used to explore the effectiveness and pathogenesis of N,N-dimethyl-3β-hydroxycholenamide (DMHCA)-treated mice with RIR injury and DMHCA-treated microglia after oxygen and glucose deprivation/reoxygenation (OGD/R).
Results
DMHCA could suppress inflammatory gene expression and attenuate neuronal lesions, restoring the retinal structure in vivo. Using scRNA-seq on the retina of DMHCA-treated mice, we provided novel insights into RIR immunity and demonstrated nerve injury-induced protein 1 (Ninjurin1/Ninj 1) as a promising treatment target for RIR. Moreover, the expression of Ninj1, which was increased in RIR injury and OGD/R-treated microglia, was downregulated in the DMHCA-treated group. DMHCA suppressed the activation of the nuclear factor kappa B (NF-κB) pathways induced by OGD/R, which was undermined by the NF-κB pathway agonist betulinic acid. Overexpressed Ninj1 reversed the anti-inflammatory and anti-apoptotic function of DMHCA. Molecular docking indicated that for Ninj1, DMHCA had a low binding energy of − 6.6 kcal/mol, suggesting highly stable binding.
Conclusion
Ninj1 may play a pivotal role in microglia-mediated inflammation, while DMHCA could be a potential treatment strategy against RIR injury.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Science and Technology Program of Guangzhou
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Neurology,Immunology,General Neuroscience
Cited by
1 articles.
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