MiRNA-494 enhances M1 macrophage polarization via Nrdp1 in ICH mice model

Journal of Inflammation

Qijiang Xiong¹  Ling Yang¹  Zhongyan Huang¹  Changlong Zhou¹  Zhao Yang¹  Wang Zhao¹  Kunlong Ma²  Gaohai Shao² 

[1] Department of Neurology and Chongqing key laboratory of cerebravascular disease, Yongchuan Hospital, Chongqing Medical University;Department of orthopedics, Yongchuan Hospital, Chongqing Medical University;

关键词: MiRNA-494;    Macrophage;    Polarization;    Nrdp1;    ICH;   

DOI  :  10.1186/s12950-020-00247-3

来源: DOAJ

【 摘 要 】

Abstract Background Ubiquitination-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. Methods In 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. Results We 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. Conclusions Taken 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.

【 授权许可】

Unknown