Abstract
BackgroundUbiquitination-mediated M1/M2 macrophage polarization plays important roles in the pathogenesis of immune disease. However, the regulatory mechanism of ubiquitination during M1/M2 macrophage polarization following intracerebral hemorrhage (ICH) has not been well studied.MethodsIn the experiment, macrophages were administered with erythrocyte lysates, and then miR-494-, Nrdp1-, and M1/M2-related markers were analyzed. Brain inflammatory response, brain edema, and neurological functions of ICH mice were also assessed.ResultsWe found that miR-494 levels increased while Nrdp1 levels decreased in macrophages after ICH. We also demonstrated that miR-494 inhibited Nrdp1 expression by directly binding its 3′-untranslated region. MiR-494 attenuated C/EBP-β activation and downstream proinflammatory factor production. Upregulation of Nrdp1 in macrophages significantly promoted M2 macrophage polarization via ubiquitinating and activating C/EBP-β. Moreover, the results indicated that miR-494 could enhance M1 macrophage polarization, promote brain edema, and impair neurological functions in ICH mice.ConclusionsTaken together, our results demonstrated that Nrdp1 contributed to M1/M2 macrophage polarization and neuroinflammation via ubiquitination and activation of C/EBP-β in ICH. miR-494 may provide a promising therapeutic clue for ICH.
Highlights
Intracerebral hemorrhage (ICH) accounts for approximately 10 to 20% of all acute cerebrovascular diseases and is associated with high mortality and disability [1]
We aimed to investigate whether miRNAs were involved in the regulation of M1/M2 macrophage polarization via Nrdp1 following intracerebral hemorrhage (ICH)
MiR-494 levels of macrophages or perihematoma tissue (The liquid accumulation surrounding ICH which appears as hypodensity around the hematoma on CT scan) were detected by real-time polymerase chain reaction (PCR) following erythrocyte lysates treatment or ICH
Summary
Intracerebral hemorrhage (ICH) accounts for approximately 10 to 20% of all acute cerebrovascular diseases and is associated with high mortality and disability [1]. Preclinical and clinical evidence suggests that inflammatory response contributes to secondary brain damage following ICH, which is characterized by the accumulation and activation of inflammatory cells and production of inflammatory factors [2]. Much evidence suggests that macrophage-mediated inflammatory response plays an important role in hemorrhagic brain damage [3, 4]. M1 phenotype macrophages release proinflammatory mediators and leads to tissue damage. M2 phenotype macrophages generate antiinflammatory cytokines and contribute to neuroprotective properties [6,7,8]. Ubiquitination-mediated M1/M2 macrophage polarization plays important roles in the pathogenesis of immune disease. The regulatory mechanism of ubiquitination during M1/M2 macrophage polarization following intracerebral hemorrhage (ICH) has not been well studied
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